血红素氧合酶的干预对糖尿病大鼠结肠动力障碍的影响  

Effect of interference in heme oxygenase on colonic dysfunction of diabetic rats

作　　者：吴高珏[1] 林琳[1] 张红杰[1] 李学良[1] 罗云[1] 王美峰[1] 

机构地区：[1]南京医科大学第一附属医院消化科,江苏省南京市210029

出　　处：《世界华人消化杂志》2007年第1期14-21,共8页World Chinese Journal of Digestology

基　　金：江苏省"135工程"医学重点人才基金项目;No.苏卫科教[2003]19号;江苏省自然科学基金项目;No.BK2004158~~

摘　　要：目的:探讨血红素氧合酶(heme oxygenase,HO)的干预对糖尿病(diabetes mellitus,DM)大鼠结肠动力障碍的影响.方法:链脲佐菌素ip建立DM模型,饲养6wk时以碳沫推进实验证实DM大鼠存在胃肠慢传输运动后,所有大鼠分为正常对照组、DM未干预组、DM+Hemin组[予HO诱导剂正铁血红素(Hemin)]及DM+ZnPP组[予HO阻滞剂锌原卟啉(zinc protoporphyrin Ⅸ,ZnPP Ⅸ)];监测体质量、血糖.饲养9wk时再测胃肠推进率,离体肌条实验记录结肠平滑肌条自发收缩反应及对Ach的反应性,Western blot及免疫组化检测近、远端结肠HO的表达.结果:6wk时DM大鼠胃肠慢传输运动模型建立.HO干预对DM大鼠体质量、血糖无影响(P>0.05).9wk时Western blot示DM未干预组(1.20±0.09)、DM+Hemin组(1.08±0.11)及DM+ZnPP组(1.10±0.08)近端结肠HO-2表达无显著差异(P>0.05),但均较正常对照组(1.66±0.14)显著减少(P<0.05);各实验组远端结肠HO-2表达无差异.正常对照组与DM未干预组近、远端结肠HO-1的表达无差异(Western blot示HO-1/α-tubulin:近端结肠0.22±0.02vs0.22±0.03;远端结肠0.23±0.03vs0.23±0.03,P>0.05);DM+Hemin组结肠HO-1的表达(近端结肠0.66±0.09;远端结肠0.47±0.07)较前两组显著增多(P<0.05);DM+ZnPP组结肠HO-1基本无表达.DM+Hemin组胃肠推进指数(54.4%±2.9%vs63.0%±1.2%,P<0.05)、结肠平滑肌条自发收缩频率、波幅和对Ach的反应性较DM未干预组显著下降(P<0.05),而DM+ZnPP组胃肠推进指数(72.5%±2.6%vs63.0%±1.2%,P<0.05)、结肠平滑肌条自发收缩频率、波幅和对Ach的反应性较DM未干预组明显改善(P<0.05).结论:HO干预(诱导或阻断),对DM大鼠体质量、血糖无影响.诱导HO-1使DM大鼠慢传输型结肠动力障碍加重,而阻断HO-1可能改善DM大鼠慢传输型结肠动力障碍.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

关 键 词：血红素氧合酶 糖尿病 结肠动力障碍 正铁血红素 锌原卟啉 

分 类 号：R587.2[医药卫生—内分泌] R574.62[医药卫生—内科学]