ATP合成酶β亚单位在PCOS伴2型糖尿病大鼠胰岛中的表达

Expression of the ATP synthase β-subunit in pancreas of rats with polycystic ovary syndrome and type 2 diabetes

目的研究ATP合成酶β亚单位在多囊卵巢综合征(PCOS)伴2型糖尿病的大鼠胰岛中的表达情况,初步探讨ATP合成酶β亚单位在PCOS发展为2型糖尿病中的作用。方法 30只雌性SD大鼠平均分为3组:PCOS组、PCOS伴2-DM组和对照组。采用硫酸普拉睾酮钠诱导PCOS模型(PCOS组,10只),硫酸普拉睾酮钠联合高脂高糖+链脲左菌素(STZ)诱导2型糖尿病大鼠模型(PCOS伴2-DM组,10只)。HE染色光镜下观察PCOS大鼠卵巢的病理结构改变,用酶联免疫吸附法测定血清睾酮(T)、雌二醇(E2)及空腹血糖(FBG)、空腹胰岛素(FINS)含量。采用免疫组织化学法检测PCOS组、PCOS伴2型糖尿病组及空白对照组胰腺胰岛中ATP合酶β亚单位的表达。结果与对照组相比,PCOS伴2-DM组及PCOS组卵巢均呈多囊样改变;与对照组相比,PCOS伴2-DM组和PCOS组大鼠FINS虽显著降低(P<0.05),但HOMA-IR指数均显著增高(P<0.05),PCOS伴2-DM组大鼠空腹血糖均≥16.7mmol/L;PCOS组及PCOS伴2-DM组大鼠血清T与E2水平显著高于对照组(P<0.05),而PCOS组及PCOS伴2-DM组之间无显著差异(P>0.05);PCOS伴2-DM组的胰岛面积显著小于对照组及PCOS组(P<0.05);PCOS伴2-DM组ATP合酶β亚单位的表达强度显著低于对照组及PCOS组(P<0.05),PCOS组与对照组相比胰岛中ATP合酶β亚单位的表达亦显著降低(P<0.05)。结论硫酸普拉睾酮钠联合高脂高糖饮食+小剂量STZ能有效诱导PCOS伴2型糖尿病大鼠模型;PCOS及PCOS伴2型糖尿病患者胰岛中ATP合成酶β亚单位表达异常,可能是导致2型糖尿病发生的原因之一。

Objective： To investigate the expression of ATP synthase β-subunit in pancreas of the rats with polycystic ovary syndrome （PCOS） and type 2 diabetes（PCOS pus 2-DM）. Methods： Thirty female SD rats were divided into three equal groups including PCOS group, PCOS plus type 2 diabetes group and control group. The rats in PCOS group were received subcutaneous injection of sodium prasterone sulfate once daily for 25 consecutive days to induce PCOS model; and the rats in the PCOS plus 2-DM group were treated with sodium prasterone sulfate combined with high- carbohydrate/high-fat diet ＆ streptozotocin （STZ） ; while the rats in the control group were injected with water for injection at the same period. Histopathological changes of the ovaries were observed by HE staining, and fasting blood glucose （FBG）, fasting insulin （FINS）, and sex hormone levels were determined three weeks later. Light microscopy examination of pancreas and ovary were performed. The expression of ATP synthase td-subunit in pancreas was measured by immunohistochemistry staining. Results： PCOS plus 2-DM group and PCOS group showed polycystic-like changes in the ovary. Compared with the control group, FINS was significantly lower, but HOMA-IR was significantly higher in PCOS plus 2-DM group and PCOS group （P〈0.05）. The FBG levels were more than or equal to 16.7 mmol/L in PCOS plus 2-DM group. The serum testosterone and estradiol levels were significantly increased in PCOS group and PCOS plus 2-DM group compared with those in control group （P〈0.05）, while there was no significant difference between PCOS group and PCOS plus 2-DM group （P〉0.05）. The islet area in PCOS plus 2-DM group was significantly less than that in control group or PCOS group（P〈0.05）. Additionally, the expression of ATP synthase β-subunit in pancreas in PCOS plus 2-DM group was significantly decreased than that in control group or PCOS group（P〈0.05）, and the expression in PCOS group was also significantly lower than in the control groups（P〈0.05）. Conclusions： The sodium prasterone sulfate combing with high-carbohydrate/high-fat diet ＆ STZ can effectively induce a model of PCOS with type 2 diabetes. The ATP synthase β-subunit of pancreas may play an important role in the pathogenesis of type 2 diabetes.