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目的:探讨硫化氢(H2S)合成酶抑制剂DL-炔丙基甘氨酸(PAG)对其2型糖尿病(T2DM)大鼠胰岛β细胞功能和凋亡相关蛋白的影响。方法:采用高糖高脂饮食喂养和腹腔注射小剂量STZ的方法建立大鼠T2DM模型,将成模大鼠按随机数字表法随机分为糖尿病组(DM组),糖尿病+DL-炔丙基甘氨酸组(DM+PAG组),另设正常对照组,各15只。每日固定时间腹腔注射受试制剂,DM+PAG组给予PAG[50 mg/(kg·d)],对照组和DM组给予相同体积的生理盐水,连续给药2周。投药结束后,检测各组大鼠空腹血糖(FBG)、血浆胰岛素(FIns)水平,胰腺组织中H2S水平,免疫组化法检测分析胰腺组织胰岛素、Caspase-3、Bax和Bcl-2的表达情况,并计算胰腺组织相对β细胞数量和平均β细胞面积。结果:与对照组相比,DM组大鼠血浆FIns降低,FBG升高,胰腺组织H2S浓度水平升高;胰腺组织胰岛素阳性颗粒减少,Caspase-3、Bax表达增强,Bcl-2的表达减弱,Bc1-2/Bax比值降低;相对β细胞数量和平均β细胞面积均明显减小;经PAG处理后,大鼠血浆FIns明显升高,FBG降低,胰腺组织H2S浓度明显降低;胰腺组织胰岛素阳性颗粒明显增多,Caspase-3、Bax表达减弱,Bcl-2的表达增强,Bc1-2/Bax比值升高;相对β细胞数量和平均β细胞面积增加。结论:内源性H2S通过调节胰岛β细胞凋亡相关蛋白表达,促进胰岛β细胞的凋亡,减少2型糖尿病大鼠胰岛β细胞的相对数量,从而减少胰岛素的分泌;而PAG能减少胰岛β细胞凋亡,增加2型糖尿病大鼠胰岛β细胞的相对数量,增加胰岛素的分泌,达到控制血糖的目的。
Objective: To investigate the effects of hydrogen sulfide (H2S) synthetase inhibitor DL-propargylglycine (PAG) on pancreatic β-cell function and apoptosis-related proteins in type 2 diabetic rats. Methods: T2DM model was established by high-fat and high-fat diet feeding and intraperitoneal injection of low-dose STZ. The rats were randomly divided into diabetic group (DM group), DM + DL-propargyl glycine Group (DM + PAG group), another set of normal control group, each 15. The rats in the DM + PAG group were given PAG [50 mg / (kg · d)] at the same time every day. The control group and the DM group were given the same volume of normal saline for 2 weeks. After the administration, the fasting blood glucose (FBG), FIns and the level of H2S in pancreas were detected and the expressions of insulin, Caspase-3, Bax and Bcl-2 in pancreas were detected by immunohistochemistry , And calculated relative pancreatic β cell number and average β cell area. Results: Compared with the control group, the plasma FIns, the FBG and the concentration of H2S in the pancreas increased significantly in the DM group. The insulin-positive granules in the pancreas decreased, the expression of Caspase-3 and Bax increased, the expression of Bcl- The ratio of Bc1-2 / Bax decreased; the number of relative β-cells and the average β-cell area decreased significantly; after treatment with PAG, FIns in plasma increased significantly, FBG decreased and the concentration of H2S in pancreatic tissue decreased significantly; The expression of Caspase-3, Bax decreased, the expression of Bcl-2 increased, the ratio of Bc1-2 / Bax increased, the number of relative β cells and the average area of β cells increased. CONCLUSION: Endogenous H2S can reduce the insulin secretion by regulating the expression of apoptosis-related proteins in pancreatic β-cells, promoting the apoptosis of pancreatic β-cells and decreasing the relative number of pancreatic β-cells in type 2 diabetic rats. However, Apoptosis, increase the relative number of pancreatic β-cells in type 2 diabetic rats, increase insulin secretion, to achieve the purpose of controlling blood sugar.