可溶性环氧化物水解酶抑制剂的降血糖功效研究

Hypoglycemic Effect of Soluble Epoxide Hydrolase Inhibitors on Diabetic Mice

为探究可溶性环氧化物水解酶抑制剂(soluble epoxide hydrolase inhibitors,sEHI)的降血糖功效,试验以高脂饲料与链脲佐菌素(streptozotocin,STZ)联合诱导的Ⅱ型糖尿病小鼠为研究对象,将C57BL/6J小鼠随机分为:正常对照组、糖尿病模型组和sEHI组,sEHI组饲喂高脂饲料,每日灌胃sEHI(t-AUCB)1 mg/kg,连续灌胃4周;糖尿病模型组饲喂高脂饲料,每日灌胃同等计量的生理盐水;正常对照组饲喂普通饲料,每日灌胃同等体积的生理盐水。期间各组小鼠均自由采食及饮水,记录小鼠体重、血糖并进行口服葡萄糖耐量试验。试验结束后,测定血清血脂指标、肝脏过氧化指标并对小鼠胰岛组织进行病理学分析。结果显示,与糖尿病模型组相比,采用sEHI干预后糖尿病小鼠的空腹血糖显著降低(P<0.05),而葡萄糖耐量水平升高;小鼠血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)水平明显降低,其中TC、TG水平与糖尿病模型组相比差异显著(P<0.05),而高密度脂蛋白与胆固醇比值(HDL/TC)水平则显著升高(P<0.05);与糖尿病模型组相比,sEHI干预组小鼠肝脏的超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性显著提高(P<0.05),丙二醛(MDA)活性显著降低(P<0.05);小鼠的胰岛组织切片分析结果表明,sEHI对小鼠胰岛组织有明显的修复作用。综上所述,sEHI具有降血糖、减轻自由基损伤、抑制脂质过氧化、修复受损胰岛组织的作用。

In order to study the hypoglycemic effect of soluble epoxide hydrolase inhibitors(sEHI)on diabetic mice,the diabetic mice model were successfully induced by high fat diet and streptozotocin(STZ).The diabetic mice(C57BL/6J)were randomly divided into three groups,including normal control group,diabetic control group and sEHI group,the mice in three groups were fed high fat diet+1mg/kg sEHI(t AUCB),high fat diet+same volume normal saline,normal diet+same volume normal saline,respectively,and intervention last for4weeks.During the experiment,the body weight,blood glucose were recorded,and performed oral glucose tolerance test was conducted.After the experiment,indicators of serum lipids,liver peroxidation and pathological analysis of pancreatic tissue were measured.The results showed that compared with diabetic control group,the fasting blood glucose of mice in sEHI group was significantly reduced(P<0.05),and their glucose tolerance was improved.And the TC(P<0.05),TG(P<0.05)and LDL(P>0.05)in sEHI group were decreased,while the LDL/TC was significantly increased(P<0.05).The SOD and CAT activity in liver of diabetic mice treated with sEHI were significantly increased(P<0.05)and MDA activity was significantly decreased(P<0.05).Based on mouse pancreatic tissue sections,we speculated that sEHI had ability to repair activity on damaged islet tissue.In conclusion,the sEHI could reduce the blood glucose level and the free radical damage,inhibit lipid peroxidation,repair of damaged islet tissue in mice.