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Yan-Jun
Zeng, Xiao-Hu Xu, Hong Xu, Chuan-Qing Xu, Forensic Medicine
Department, Medical College, Santou University, Santou 515031,
Guangdong Province, China
Jian Yang, En-Ping Zhang, Beijing University of Technology,
Beijing 100022, China
Jing-Bo Zhao, Dong-Hua Liao, Hans Gregersen, Department of
Gastrointestinal Surgery, Aalborg University, Denmark
Correspondence to: Yan-Jun Zeng, Forensic Medicine
Department, Medical College, Shantou University, Shantou 515031,
Guangdong Province, China. yjzeng@bjut.edu.cn
Telephone: +86-10-67391685
Fax: +86-10-67391738
Received: 2003-8-26
Accepted: 2003-10-22
Abstract
AIM: To study morphologic and biomechanical changes of
oesophagus in diabetes rats.
METHODS: Diabetes was induced by a single injection of
streptozotocin (STZ). The type of diabetes mellitus induced by
parenteral STZ administration in rats was insulin-dependent (type
I). The samples were excised and studied in vitro using a
self-developed biomaterial test machine.
RESULTS: The body mass was decreased after 4 d with STZ treatment.
The length of esophagus shortened after 4, 7, 14 d. The opening
angle increased after 14 d. The shear, longitudinal and
circumferential stiffness were obviously raised after 28 d of STZ
treatment.
CONCLUSION: The changes of passive biomechanical properties reflect
intra-structural alteration of tissue to a certain extent. This
alteration will lead to some dysfunction of movement. For example,
tension of esophageal wall will change due to some obstructive
disease.
Zeng YJ, Yang J, Zhao
JB, Liao DH, Zhang EP, Gregersen H, Xu XH, Xu H, Xu CQ. Morphologic
and biomechanical changes of rat oesophagus in experimental
diabetes. World J Gastroenterol
2004; 10(17): 2519-2523
http://www.wjgnet.com/1007-9327/10/2519.asp
INTRODUCTION
Esophagus is a distensible muscular tube that connects pharynx
and stomach. The function of the esophagus is to transport food by
peristaltic movement, which is the result of the interaction of the
tissue forces in the esophageal wall and the hydrodynamic forces in
the food bolus. Esophagus has been studied by radiography[1],
concurrent videofluoroscopy and manometry[2,3],
high-frequency ultrasonography[4-6], and endoscopic
sclerotherapy[7,8]. Motility disorders[9],
bolus transport[10,11], systemic sclerosis[12],
pain[13], wall distensibility[8], impedance
planimetric characterization[14] and the effects of
epidermal growth factor[15] on esophagus have been
reported in many papers. Since the function of esophagus is mainly
mechanical, our work was focused on providing quantitative
measurement of passive biomechanical properties of esophagus. Many
investigations on biomechanics of esophagus are available in the
literature[16,17]. Gregersen et al. studied strain
distribution in the layered wall[18,19], relation between
pressure and cross-sectional area[20] and other
biomechanical properties[21-23] of esophagus. A more
recent work used a novel ultrasound technique to study the
biomechanics of the human esophagus in vivo[24].
Patel represented biomechanical and sensory parameters of the human
esophagus at four levels[25]. Researchers have done a lot
biomechanical studies on gastrointestinal tract such as intestine[26,27],
small intestine[28-32], ileum[33], duodenum[34]
and large intestine[35,36].
Most previous studies
have explained the relationship between the diabetes and
gastrointestinal tract function[37,38]. Some researches
studied relationship between esophageal dysfunction and neuropathy[39],
oesophagus scintigraphy[40] and the relationship between
esophageal motility and transit[41] in diabetic patients.
More recently, Jorgensen reported tension-strain relations and
morphometry of rat small intestine in experimental diabetes[42].
Zhao introduced the remodeling of zero-stress state of small
intestine in streptozotocin-induced diabetic rats[43].
This paper presents the
effect of experimental diabetes on the morphologic and biomechanical
properties of the esophagus. The result of this study indicated that
experimental type I diabetes caused significant changes in the
passive biomechanical properties in the rat esophagus.
MATERIALS AND METHODS
Materials
Diabetes was induced by a single injection of streptozotocin
(STZ). The form of diabetes mellitus induced by parenteral STZ
administration in rats is insulin-dependent (type I). Twenty-seven
rats were divided into 4 groups according to the survival time after
STZ treatment: 4 d (n = 7), 7 d (n = 7), 14 d (n =
7), 28 d (n = 6). Another 8 rats were used as normal
controls. The samples were taken from the middle part of esophagus.
Two rings were cut from each end of the sample to measure the
geometric parameters of the no-load state and the opening angle at
zero-stress state. The remaining part was excised and studied in
vitro using a self-developed biomaterial test machine.
Methods
Using this machine, the esophagus was stepwise elongated and
inflated and continuously twisted in circumferential-longitudinal
direction. In the normal controls and 28 d of diabetes group, after
the intact esophagus was tested, the mucosa and muscle layers were
separated using microsurgery and tested in the same loading
procedure as mentioned above. The esophagus was treated as a
membrane when the stress and strain were calculated, the
longitudinal and circumferential stresses were considered to be
evenly distributed along the wall thickness while the radial stress
and other transverse shear stresses were ignored. The torque vs
twist-angle relation was approximately linear at a specified
pressure and longitudinal stretch ratio. Thus, the shear modulus can
be computed by the torque, twist angle and polar moment of inertial
at this state. However, the shear modulus varied greatly with the
changing inflation pressure and longitudinal stretch ratio.
Figure 1(PDF)
Simplified diagram of biomaterial test machine.1: Linear
stage, 2: Torque transducer, 3: Organ bath, 4: Specimen, 5: Force
transducer, 6: Motor for axial rotation, 7: Pressure transducer, 8:
Infusion channel, 9: Motor for linear stage, 10: Rails for linear
stage, 11: CCD camera, 12: Plastic rod.
RESULTS
Type I diabetes could induce the following effect on the
biomechanical and morphologic properties of esophagus: body weight
and morphology, shear modulus, circumferential and longitudinal
stress-strain relationship, stress-strain relationship of muscle
layer and mucosa layer.
Body weight and morphology
The body mass
kept a steady increase in the control rats. But it went down after 4
d in the diabetes rat (Figure 2A). The length of esophagus in vivo
obviously declined after 4, 7, 14 d, but it would return to normal
level after 28 d (Figure 2B). The mass per unit lengh in vitro
changed little (Figure 2C). In the intact esophagus, the opening
angle increased after 14 d of STZ treatment (Figure 2D).
Figure
2(PDF)
Changes of body mass and esophagus morphology and opening
angle at zero-stress state in the process of diabetes development.
Dunner’s
test result: significant difference vs normal control (aP<0.05).
A: Change of body mass, B: Change of in vivo length, C:
Change of mass per unit length, D: Change of opening angle.
Shear
modulus
Changes of elastic shear moduli in the course of diabetes
development at longitudinal stretch ratio lzz = 1.5 and various transmural pressure are shown in
Figure 3A. Elastic shear modulus would rise with increased
transmural pressure. Especially when transmural pressure was more
than 0.25 kPa, the shear moduli for various transmural pressure were
remarkably different. And diabetes has notably affected the shear
modulus. This effect showed that shear moduli are obviously
increased after 28 d.
Changes of elastic shear
modulus in the course of diabetes development at transmural pressure
P = 1 kPa and various longitudinal stretch ratio are pictured
in Figure 3B. Elastic shear modulus would rise with increased
longitudinal stretch ratio. Shear moduli were remarkably different
at various longitudinal stretch ratios. And diabetes has notably
affected the shear modulus. This effect demonstrated that shear
moduli were obviously increased after 28 d of STZ treatment.
Circumferential and
longitudinal stress-strain relationship
Figure 4A shows the changes of circumferential stress-strain
relationship in the course of diabetes development at longitudinal
stretch ratio lzz = 1.5 and various transmural pressure. All curves
of experimental group inclined to left side except that after 4 d.
The curve after 28 d was on the most left side. The circumferential
stiffness increased after 7, 14, 28 d of diabetes.
The changes of
longitudinal stress-strain relationship in the course of diabetes
development at transmural pressure P = 0.25 kPa and various
longitudinal stretch ratio are pictured in Figure 4B.The
stress-strain curve after 28 d was obviously inclined to left side.
So the longitudinal stiffness notably increased after 28 d.
Stress-strain relationship
of muscle layer and mucosa layer
The circumferential stress-strain relationship of muscle
layer and mucosa layer in the process of inflation at a longitudinal
stretch ratio of 1.5 is pictured in Figure 5A. And the experimental
diabetes was after 28 d. For muscle layer, there was no obvious
difference between the control and diabetes groups. For mucosa
layer, the stress-strain curve moved to left side in parallel. So
circumferential stiffness of mucosa layer with diabetes was larger
than that of control.
Figure 5B shows
longitudinal stress-strain relationship of muscle layer and mucosa
layer in the process of elongation at a transmural pressure of 0.25
kPa. For muscle layer, there was no obvious difference between
control and diabetes groups. There was no notable difference for
mucosa layer either.
Figure
3(PDF) Change
of elastic shear modulus in the process of diabetes development. A:
Change at lzz
= 1.5 and various transmural pressure, B: Change at P
= 1 kPa and various longitudinal stretch ratio.
Figure 4(PDF)
A: Change of circumferential stress-strain relation in
the course of diabetes development at lzz
= 1.5 and various transmural pressure. B: Change of
longitudinal stress-strain relation in the course of diabetes
development at P = 0.25 kPa and various longitudinal stretch
ratio.
Figure
5(PDF)
A:
Circumferential stress-strain relation between muscle layer and
mucosa layer in the process of inflation at a longitudinal stretch
ratio of 1.5. N: Normal control, D: 28 d of diabetes. B: Longitudinal
stress-strain relation between muscle layer and mucosa layer in the
process of elongation at a transmural pressure of 0.25 kPa. N:
Normal control, D: 28 d of diabetes.
DISCUSSION
A large number of studies have discovered that diabetes can
affect the movement of oesophagus. Transportation of oesophagus may
delay or slow down, and movement of esophagus can not coordinate.
This dysfunction of
movement can be a result of muscle and nerve cooperative failure[39-41,44-47].
Histologic research has proved that diabetes can destroy vagus nerve[48].
Though there are many papers on movement and function of oesophagus
in diabetes, few data on morphologic and passive biomechanical
properties are seen. The change of passive biomechanical properties
reflects intra-structural alteration of tissue to a certain extent.
This alteration will result in some dysfunction of movement, for
example, tension of esophageal wall will change due to some
obstructive disease[49,50], and therefore, it is
necessary to study biomechanics and morphology together.
The body mass is
decreased in rat with diabetes. This is consistent with other
studies[43,51]. Diabetes will lead to hyperplasia of some
organs. Hyperplasia of esophagus is less frequent than that of small
intestine[52,53]. Diabetes has caused rise of the opening
angle of small intestine[44], also it is seen for
esophagus.
In this paper, the shear,
longitudinal and circumferential stiffnesses were obviously elevated
after 28 d with STZ treatment. Jorrensen[42], Liu[54]
and Zhao[51] have discovered that stiffness is raised in
diabetes in small intestine, blood vessel and arterial wall.
We can draw a conclusion
that the changes of passive biomechanical properties reflect
intra-structural alteration of tissue to a certain extent. This
alteration will lead to some dysfunction of movement.
REFERENCES
1
Grishaw EK, Ott DJ, Frederick MG, Gelfand DW, Chen MY.
Functional abnormalities of the esophagus: a prospective
analysis of radiographic findings
relative to age and symptoms. Am J Roentgenol 1996; 167: 719-723
2
Pouderoux P, Shi G, Tatum RP, Kahrilas PJ. Esophageal solid
bolus transit: studies using concurrent videofluoroscopy
and manometry. Am J Gastroenterol
1999; 94: 1457-1463
3
Narawane NM, Bhatia SJ, Mistry FP, Abraham P, Dherai AJ.
Manometric mapping of normal esophagus and definition of
the transition zone. Indian J
Gastroenterol 1998; 17: 55-57
4
Nicosia MA, Brasseur JG, Liu JB, Miller LS. Local
longitudinal muscle shortening of the human esophagus from
high-frequency ultrasonography. Am J
Physiol Gastrointest Liver Physiol 2001;
281: G1022-1033
5
Pehlivanov N, Liu J, Kassab GS, Puckett JL, Mittal RK.
Relationship between esophageal muscle thickness and
intraluminal pressure: an
ultrasonographic study. Am J Physiol Gastrointest Liver Physiol
2001; 280: G1093-1098
6
Assentoft JE, Gregersen H, O'Brien WD Jr. Determination of
biomechanical properties in guinea pig esophagus by
means of high frequency ultrasound
and impedance planimetry. Dig Dis Sci 2000; 45: 1260-1266
7
Juhl CO, Vinter-Jensen L, Djurhuus JC, Gregersen H, Dajani EZ.
Biomechanical properties of the oesophagus damaged
by endoscopic sclerotherapy. An
impedance planimetric study in minipigs. Scand J Gastroenterol 1994;
29: 867-873
8
Petersen JA, Djurhuus C, Koff J, Vinter-Jensen L, Gregersen
H. Endoscopic sclerotherapy in porcine esophagus changes
luminal cross-sectional area and wall
distensibility dose- and time-dependently. Dig Dis Sci 1998; 43:
521-528
9
Hewson EG, Ott DJ, Dalton CB, Chen YM, Wu WC, Richter JE.
Manometry and radiology. Complementary studies in the
assessment
of esophageal motility disorders. Gastroenterology 1990; 98: 626-632
10
Nicosia MA, Brasseur JG. A mathematical model for estimating
muscle tension in vivo during esophageal bolus transport.
J
Theor Biol 2002; 219: 235-255
11
Ren J, Massey BT, Dodds WJ, Kern MK, Brasseur JG, Shaker R,
Harrington SS, Hogan WJ, Arndorfer RC. Determinants
of intrabolus pressure during
esophageal peristaltic bolus transport. Am J Physiol 1993; 264(3 Pt
1): G407-413
12
Villadsen GE, Storkholm J, Zachariae H, Hendel L, Bendtsen F,
Gregersen H. Oesophageal pressure-cross-sectional area
distributions and secondary
peristalsis in relation to subclassification of systemic sclerosis.
Neurogastroenterol Motil
2001; 13: 199-210
13
Drewes AM, Schipper KP, Dimcevski G, Petersen P, Andersen OK,
Gregersen H, Arendt-Nielsen L. Multimodal
assessment of pain in the esophagus:
a new experimental model. Am J Physiol Gastrointest Liver Physiol
2002; 283: G95-103
14
Gregersen H, Vinter-Jensen L, Juhl CO, Dajani EZ. Impedance
planimetric characterization of the distal oesophagus in
the goettingen minipig. J Biomech
1996; 29: 63-68
15
Vinter-Jensen L, Juhl CO, Eika B, Gregersen H, Dajani EZ.
Epidermal growth factor attenuates the sclerotherapy-induced
biomechanical properties of the
oesophagus. An experimental study in minipigs. Scand J Gastroenterol
1995; 30: 614-619
16
Gregersen H, Weis SM, McCulloch AD. Oesophageal morphometry
and residual strain in a mouse model of osteogenesis
imperfecta. Neurogastroenterol Motil
2001; 13: 457-464
17
Gregersen H, Lee TC, Chien S, Skalak R, Fung YC. Strain
distribution in the layered wall of the esophagus. J Biomech
Eng 1999; 121: 442-448
18
Lu X, Gregersen H. Regional distribution of axial strain and
circumferential residual strain in the layered rabbit
oesophagus. J Biomech 2001; 34:
225-233
19
Liao D, Fan Y, Zeng Y, Gregersen H. Stress distribution in
the layered wall of the rat oesophagus. Med Eng Phys
2003; 25:731-738
20
Gregersen H, Christensen LL. Pressure-cross-sectional area
relations and elasticity in the rabbit oesophagus in vivo.
Digestion 1996; 57: 174-179
21
Orvar KB, Gregersen H, Christensen J. Biomechanical
characteristics of the human esophagus. Dig Dis Sci
1993; 38: 197-205
22
Barlow JD, Gregersen H, Thompson DG. Identification of the
biomechanical factors associated with the perception of
distension in the human esophagus. Am
J Physiol Gastrointest Liver Physiol 2002; 282: G683-689
23
Drewes AM, Pedersen J, Liu W, Arendt-Nielsen L, Gregersen H.
Controlled mechanical distension of the human
oesophagus: sensory and biomechanical
findings. Scand J Gastroenterol 2003; 38: 27-35
24
Takeda T, Kassab G, Liu J, Puckett JL, Mittal RR, Mittal RK.
A novel ultrasound technique to study the biomechanics of
the human esophagus in vivo. Am J
Physiol Gastrointest Liver Physiol 2002; 282: G785-793
25
Patel RS, Rao SS. Biomechanical and sensory parameters of the
human esophagus at four levels. Am J Physiol
1998; 275(2 Pt 1): G187-191
26
Dou Y, Lu X, Zhao J, Gregersen H. Morphometric and
biomechanical remodelling in the intestine after small bowel
resection in the rat.
Neurogastroenterol Motil 2002; 14: 43-53
27
Dou Y, Gregersen S, Zhao J, Zhuang F, Gregersen H.
Morphometric and biomechanical intestinal remodeling induced
by fasting in rats. Dig Dis Sci 2002;
47: 1158-1168
28
Dou Y, Gregersen S, Zhao J, Zhuang F, Gregersen H. Effect of
re-feeding after starvation on biomechanical properties
in rat small intestine. Med Eng Phys
2001; 23: 557-566
29
Zhao J, Yang J, Vinter-Jensen L, Zhuang F, Gregersen H. The
morphometry and biomechanical properties of the rat
small intestine after systemic
treatment with epidermal growth factor. Biorheology 2002; 39:
719-733
30
Liao D, Yang J, Zhao J, Zeng Y, Vinter-Jensen L, Gregersen H.
The effect of epidermal growth factor on the incremental
Young's moduli in the rat small
intestine. Med Eng Phys 2003; 25: 413-418
31
Zhao J, Yang J, Vinter-Jensen L, Zhuang F, Gregersen H.
Biomechanical properties of esophagus during systemic
treatment with epidermal growth
factor in rats. Ann Biomed Eng 2003; 31: 700-709
32
Zeng YJ, Qiao AK, Yu JD, Zhao JB, Liao DH, Xu XH, Hans G.
Collagen fiber angle in the submucosa of small intestine and
its application in Gastroenterology.
World J Gastroenterol 2003; 9:804-807
33
Yang J, Zhao JB, Zeng YJ, Gregersen H. Biomechanical
properties of ileum after systemic treatment with epithelial
growth factor. World J Gastroenterol
2003; 9: 2278-2283
34
Gao C, Zhao J, Gregersen H. Histomorphometry and strain
distribution in pig duodenum with reference to zero-stress
state. Dig Dis Sci 2000; 45:
1500-1508
35
Gao C, Gregersen H. Biomechanical and morphological
properties in rat large intestine. J Biomech
2000; 33: 1089-1097
36
Yang J, Zhao J, Zeng Y, Vinter-Jensen L, Gregersen H.
Morphological properties of zero- stress state in large
intestine
during systemic EGF treatment. Dig
Dis Sci 2003; 48: 442-448
37
Murtagh JE. Diabetes mellitus: the general practitioner's
perspective. Clin Exp Optom 1999; 82: 74-79
38
Verne GN, Sninsky CA. Diabetes and the gastrointestinal
tract. Gastroenterol Clin North Am 1998; 27: 861-874
39
Kinekawa F, Kubo F, Matsuda K, Fujita Y, Tomita T, Uchida Y,
Nishioka M. Relationship between esophageal dysfunction
and neuropathy in diabetic patients.
Am J Gastroenterol 2001; 96: 2026-2032
40
Westin L, Lilja B, Sundkvist G. Oesophagus scintigraphy in
patients with diabetes mellitus. Scand J Gastroenterol
1986; 21: 1200-1204
41
Holloway RH, Tippet MD, Horowitz M, Maddox AF, Moten J, Russo
A. Relationship between esophageal motility and
transit in patients with type I
diabetes mellitus. Am J Gastroenterol 1999; 94: 3150-3157
42
Jorgensen CS, Ahrensberg JM, Gregersen H, Flyvberg A.
Tension-strain relations and morphometry of rat small
intestine in experimental diabetes.
Dig Dis Sci 2001; 46: 960-967
43
Zhao J, Sha H, Zhou S, Tong X, Zhuang FY, Gregersen H.
Remodelling of zero-stress state of small intestine in
streptozotocin-induced diabetic rats.
Effect of gliclazide. Dig Liver Dis 2002; 34: 707-716
44
Karayalcin B, Karayalcin U, Aburano T, Nakajima K, Hisada K,
Morise T, Okada T, Takeda R. Esophageal clearance
scintigraphy, in diabetic patients-a
preliminary study. Ann Nucl Med 1992; 6: 89-93
45
Sundkvist G, Hillarp B, Lilja B, Ekberg O. Esophageal motor
function evaluated by scintigraphy, video-radiography and
manometry in diabetic patients. Acta
Radiol 1989; 30: 17-19
46
Clouse RE, Lustman PJ, Reidel WL. Correlation of esophageal
motility abnormalities with neuropsychiatric status in
diabetics. Gastroenterology 1986;
90(5 Pt 1): 1146-1154
47
Rathmann W, Enck P, Frieling T, Gries FA. Visceral afferent
neuropathy in diabetic gastroparesis. Diabetes Care
1991; 14: 1086-1089
48
Smith B. Neuropathology of the oesophagus in diabetes
mellitus. J Neurol Neurosurg Psychiatry 1974; 37: 1151-1154
49
Gregersen H, Giversen IM, Rasmussen LM, Tottrup A.
Biomechanical wall properties and collagen content in the
partially
obstructed opossum esophagus.
Gastroenterology 1992; 103: 1547-1551
50
Mittal RK, Ren J, McCallum RW, Shaffer HA Jr, Sluss J.
Modulation of feline esophageal contractions by bolus volume
and outflow obstruction. Am J Physiol
1990; 258(2 Pt 1): G208-215
51
Zhao J, Lu X, Zhuang F, Gregersen H. Biomechanical and
morphometric properties of the arterial wall referenced to the
zero-stress state in experimental
diabetes. Biorheology 2000; 37: 385-400
52
Mayhew TM, Carson FL, Sharma AK. Small intestinal morphology
in experimental diabetic rats: a stereological study
on the effects of an aldose reductase
inhibitor (ponalrestat) given with or without conventional insulin
therapy.
Diabetologia 1989; 32: 649-654
53
Zoubi SA, Williams MD, Mayhew TM, Sparrow RA. Number and
ultrastructure of epithelial cells in crypts and villi along
the streptozotocin-diabetic small
intestine: a quantitative study on the effects of insulin and aldose
reductase inhibition.
Virchows Arch 1995; 427: 187-193
54
Liu SQ, Fung YC. Changes in the rheological properties of
blood vessel tissue remodeling in the course of development
of diabetes. Biorheology 1992; 29:
443-457
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