酮替芬对链脲佐菌素诱导的糖尿病模型大鼠胰岛功能的影响

目的:探讨酮替芬对链脲佐菌素诱导的糖尿病模型大鼠胰岛功能的影响及其作用机制.方法:以高糖高脂饲料对SD大鼠饮食诱导6周,随后一次性i.p.给予链脲佐菌素(STZ)制备糖尿病大鼠模型.模型建立后,实验组给予酮替芬0.09 mg·kg-1·d-1,分别在第0、4、8周宰杀实验大鼠,检测空腹血糖(FBG)、空腹胰岛素(FINS),计算胰岛素敏感指数(ISI)、胰岛素抵抗指数(HOMA-IR),检测炎症因子IL-6、TNF-α,并留取胰腺组织,制片染色进行光镜、电镜观察.分离胰岛细胞线粒体,检测细胞色素C氧化酶(Cytochrome C oxidase,CCO)、琥珀酸脱氢酶(Succinate dehydrogenase,SDH)活性.结果:酮替芬降低糖尿病大鼠的血糖水平(P＜0.05),增加ISI和降低HOMA-IR(P＜0.01),降低IL-6和TNF-α水平,增加胰腺组织中CCO和SDH活性(P＜0.01),还可以改善胰岛细胞形态结构.结论:酮替芬能改善糖尿病大鼠的胰岛功能,其作用机制可能是通过抑制NF-кB激活实现抗炎及改善β细胞线粒体的能量代谢.

Effect of Ketotifen on pancreatic function of streptozotocin-induced type 2 diabetic rats

Abstract： OBJECTIVE To investigate the effect and mechanism of Ketotifen on pancreati-c function of streptozotocin-induced type 2 diabetic rats. METHODS Male SD rats werefed with high-carbon hydrate-fat diet 6 weeks and ip given STZ to induce a type 2 diab-etes model. Rats of Ketotifen group were fed with Ketotifen 0.09mg/kg？d,and killed in batches in different time（o,4th,8th week）to test the fasting blood glucose（FBG）、fasting pl-asma insulin（FINS）, and calculated the insulin sensitivity index（ISI） and homeostasis mo-del assessment insulin resistance index（HOMA-IR）,to test the level of Interleukin-6（IL-6）、t-umor nectosis factor-alpha（TNF-α）,and the pancreatic tissue were excised and observed b-y light microscope（LM） and transmission electron microscope, islet cell mitochondria wer-e separated to test the activity of cytochrome C oxidase（CCO） and succinate dehydrogenase（SDH）. RESULTS Ketotifen suppressed serum glucose in diabetic rats（P〈0.05）, increase-d ISI and reduced HOMA-IR（P〈0.01）, Ketotifen reduced serum IL-6,TNF-α, increased the activity of CCO and SDH.furthermore, Ketotifen can improve the morphological struc-ture of islet cell. CONCLUSION Ketotifen can improve the pancreatic function of strep-tozotocin-induced type 2 diabetic rats possibly by inhibition of activation of NF-κB to anti-inflammatory and improve the energy metabolism of βcell mitochondria.