Heme oxygenase-1 (HO-1) system catalyzes heme to biologically active products: carbon monoxide, biliverdin/bilirubin and free iron. It is involved in maintaining cellular homeostasis and many physiological and pathophysiological processes. A growing body of evidence indicates that HO-1 activation may play an important protective role in acute and chronic inflammation of gastrointestinal tract. This review focuses on the current understanding of the physiological significance of HO-1 induction and its possible roles in the gastrointestinal inflammation studied to date. The ability to upregulate HO-1 by pharmacological means or using gene therapy may offer therapeutic strategies for gastrointestinal inflammation in the future.

• Heme oxygenase-1
• Gastrointestinal inflammation

AIM: To investigate the effect of heme oxygenase (HO) interference on the colonic dysfunction in rats with diabetes mellitus (DM).

METHODS: DM model was established by intraperitoneal injection of streptozotocin (STZ) in Sprague and Dawley rats. Six weeks later, the diabetic rats were validated to be suffered with gastrointestinal dysfunction using charcoal (Indian ink) propulsion experiment. Then the rest rats were randomly divided into 4 groups, named group A (normal control), B (diabetic rats without interference), C (diabetic rats administrated with Hemin, the inducer of HO) and D [diabetic rats administrated with zinc protoporphyrin Ⅸ (ZnPP Ⅸ), the inhibitor of HO]. The weight and blood glucose of the rats were tested. Three more weeks later, the motilities of the strips isolated from the proximal and distal colon were recorded. The level of HO in the colon was also detected by immunohistochemistry and Western blot.

RESULTS: The model of diabetic rats suffered with gastrointestinal dysfunction was successfully duplicated. Administration of Hemin or ZnPP Ⅸ had no effect on the weight or blood glucose of diabetic rats (P > 0.05). There was no significant difference in HO-2 expression of the distal colon between the diabetic rats with or/and without interference (P > 0.05). But in comparison with the controls, HO-2 expression of the proximal colon in group B, C or D was significantly declined (Western blot: 1.20 ± 0.09, 1.08 ± 0.11, 1.10 ± 0.08 vs 1.66 ± 0.14, P < 0.05). The colonic expression of HO-1 was not significantly different between group A and B (Western blot: proximal 0.22 ± 0.02 vs 0.22 ± 0.03; distal 0.23 ± 0.03 vs 0.23 ± 0.03; both P > 0.05), but HO-1 expression was markedly higher in group C (proximal 0.66 ± 0.09; distal 0.47 ± 0.07) than that in the former two groups (P < 0.05); the expression of HO-1 was hardly found in group D. In comparison with those in group B, the gastrointestinal propulsion rate (54.4% ± 2.9% vs 63.0% ± 1.2%, P < 0.05), spontaneous contraction frequencies, amplitudes, and reaction to acetylcholine of colonic smooth muscles were dramatically declined in group C (P < 0.05), while those (gastrointestinal propulsion rate: 72.5% ± 2.6% vs 63.0% ± 1.2%, P < 0.05) in group D were markedly improved (all P < 0.05).

CONCLUSION: HO interference has no effect on the body weight or blood glucose of diabetic rats. The induction of HO-1 may aggravate the decline of colonic motility in diabetic rats, while HO-1 blockage may improve the declined colonic motility.

• Heme oxygenase
• Colonic dysfunction
• Diabetes mellitus
• Hemin
• Zinc protoporphyrin Ⅸ