关键词: 血管紧张素II 1型受体自身抗体, 硫氧还蛋白相互作用蛋白, INS-1细胞, 凋亡

Abstract: Objective Whether Angiotensin II type 1 receptor (Ang II -1R) autoantibody induces islet cell apoptosis by affecting thioredoxin - interacting protein (TXNIP) Methods In cultured rat islet cell line INS-1 cells, and the survival rate of cells was detected using the cell counting kit-8(CCK-8), the results showed 10-6 mol/L of Ang II -1R autoantibody concentration and 24 h were optimal concentration and time point; Under the above conditions, cell apoptosis and the expression of apoptotic protein was respectively detected by flow- cytometry and Western blot; the effect of Ang II -1R autoantibody on the mRNA and protein level of TXNIP was detected by Real-time PCR and Western blot. Results The results showed that Ang II -1R autoantibody decreased the activity of INS-1 cells in dose- and time-dependent manner; the apoptosis of cell was significantly increased in the Ang II -1R autoantibody group, compared with control group. TXNIP mRNA level and protein expression were also increased by Ang II -1R autoantibody treatment. After RNA interference silenced TXNIP expression of INS-1 cells, the expression of TXNIP was down-regulated, and apoptosis was also reduced. After using AT1R antagonist telmisartan (TM), the up-regulation of TXNIP and apoptosis induced by Ang II -1R autoantibody were inhibited. Conclusions Ang II -1R autoantibody can induce apoptosis of islet cells by up-regulating TXNIP expression, which may provide a new target for the prevention and treatment of patients with Ang II -1R autoantibody positive diabetes.

Key words: angiotensin II type 1 receptor autoantibodies, thioredoxin-interacting protein, INS - 1 cells, apoptosis