Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
Oxid Med Cell Longev. 2018 Dec 2;2018:8616194. doi: 10.1155/2018/8616194. eCollection 2018.
The current study was performed to investigate the effects and potential effects of irbesartan pretreatment on pancreatic -cell apoptosis in a streptozotocin- (STZ-) induced acute mouse model of prediabetes. Twenty-four male BALB/C mice (18-22 g) were randomly divided into three groups: normal control group (NC, = 6), STZ group (STZ, = 8), and irbesartan + STZ group (IRB + STZ, = 10). In the IRB + STZ group, mice were administered irbesartan (300 mg/kg per day) by gavage for one week. The STZ group and IRB + STZ group received STZ (80 mg/kg by intraperitoneal (IP) injection once). The NC group received normal saline (80 mg/kg by IP injection once). Fasting blood glucose prior to STZ injection and presacrifice was analysed using samples withdrawn from the caudal vein to confirm the induction of prediabetes. Haematoxylin and eosin staining, immunohistochemical detection of insulin, and apoptosis analysis were performed. Reverse transcription-quantitative polymerase chain reaction was used to detect angiotensin II type 1 receptor (AT1R), caspase-3, and p38 mitogen-activated protein kinase (MAPK) mRNA expression. Blood glucose was significantly higher in the STZ group (9.01 ± 1.1089 vs 4.78 ± 0.7026) and IRB + STZ group (7.86 ± 1.1811 vs 4.78 ± 0.7026) compared with the NC group ( < 0.05). In comparison to the STZ group, the islet cell damage was marginally improved in the IRB + STZ group, and the IRB + STZ group had a significantly lower apoptotic rate than the STZ group (22.42 ± 8.3675 vs 50.86 ± 5.3395, < 0.001). AT1R expression in the IRB + STZ group was lower than that in the STZ group (1.56 ± 1.2207 vs 3.92 ± 2.4392, < 0.05). The mRNA expression of caspase-3 in pancreatic tissue was significantly lower in the IRB + STZ group than in the STZ group (0.90 ± 0.7272 vs 1.88 ± 1.0572, < 0.05). Similarly, the IRB + STZ group also had lower p38MAPK levels than the STZ group (1.16 ± 1.0642 vs 2.55 ± 1.7925, > 0.05). In conclusion, irbesartan pretreatment improved glucose levels and insulin secretion and decreased islet -cell apoptosis to protect islet cells in an STZ-induced acute prediabetic mouse model.
当前研究旨在探究厄贝沙坦预处理对链脲佐菌素（STZ）诱导的急性糖尿病前期小鼠模型中胰岛细胞凋亡的影响及潜在影响。24 只雄性 BALB/C 小鼠（18-22g）被随机分为三组：正常对照组（NC，n=6）、STZ 组（STZ，n=8）和厄贝沙坦+STZ 组（IRB+STZ，n=10）。IRB+STZ 组小鼠经灌胃给予厄贝沙坦（300mg/kg/天）预处理一周。STZ 组和 IRB+STZ 组接受 STZ（80mg/kg 经腹腔内（IP）注射一次）。NC 组接受生理盐水（80mg/kg 经 IP 注射一次）。在 STZ 注射前和牺牲前，通过尾静脉抽取样本分析空腹血糖，以确认糖尿病前期的诱导。进行苏木精和伊红染色、胰岛素免疫组织化学检测和凋亡分析。采用逆转录-定量聚合酶链反应检测血管紧张素 II 型 1 型受体（AT1R）、半胱氨酸天冬氨酸蛋白酶-3（caspase-3）和 p38 丝裂原活化蛋白激酶（MAPK）mRNA 表达。与 NC 组相比，STZ 组（9.01±1.1089 比 4.78±0.7026）和 IRB+STZ 组（7.86±1.1811 比 4.78±0.7026）的血糖明显升高（<0.05）。与 STZ 组相比，IRB+STZ 组胰岛细胞损伤略有改善，且 IRB+STZ 组的凋亡率明显低于 STZ 组（22.42±8.3675 比 50.86±5.3395，<0.001）。IRB+STZ 组 AT1R 表达低于 STZ 组（1.56±1.2207 比 3.92±2.4392，<0.05）。IRB+STZ 组胰腺组织中 caspase-3 的 mRNA 表达明显低于 STZ 组（0.90±0.7272 比 1.88±1.0572，<0.05）。同样，IRB+STZ 组 p38MAPK 水平也低于 STZ 组（1.16±1.0642 比 2.55±1.7925，>0.05）。总之，厄贝沙坦预处理可改善血糖水平和胰岛素分泌，减少胰岛细胞凋亡，从而保护 STZ 诱导的急性糖尿病前期小鼠模型中的胰岛细胞。
