Department of Pharmacy, Department of Endocrinology, Changzhou No. 2 People's Hospital Affiliated with Nanjing Medical University, Changzhou, 213003, China.
Department of Pharmacology, China Pharmaceutical University, Nanjing, 210009, China.
Metab Brain Dis. 2018 Aug;33(4):1327-1334. doi: 10.1007/s11011-018-0237-z. Epub 2018 May 3.
The present study investigated the protective actions of telmisartan, an angiotensin II type 1 receptor blocker (ARBs), against the cell apoptosis induced by exposure to hydrogen peroxide (HO) in differentiated PC12 cells. Preincubation of PC12 cells with telmisartan prevented HO-induced cytotoxicity as indicated by increased MTT (3,(4,5-dimethylthiazole-2-yl)2,5-diphenyl-tetrazolium bromide) reduction, decreased lactate dehydrogenase (LDH) release, and improved morphological changes. Hoechst 33,258 staining showed that telmisartan markedly reduced shrunken nuclei of the cells, and Western blot analysis indicated that telmisartan significantly attenuated caspase-3 activity, as indicated by decreased ratio of cleaved Caspase-3 to its precursor and increased ratio of Bcl-2/Bax. The present findings showed that telmisartan protected against cellular oxidative damages by inhibiting apoptotic response.
本研究探讨了血管紧张素 II 型 1 型受体阻滞剂（ARB）替米沙坦对过氧化氢（HO）诱导分化 PC12 细胞凋亡的保护作用。替米沙坦预先孵育 PC12 细胞可预防 HO 诱导的细胞毒性，表现为 MTT（3，（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴盐）还原增加、乳酸脱氢酶（LDH）释放减少和形态变化改善。Hoechst 33,258 染色显示替米沙坦明显减少细胞皱缩的细胞核，Western blot 分析表明替米沙坦显著抑制半胱天冬酶-3 活性，表现为裂解 Caspase-3 与前体的比值降低和 Bcl-2/Bax 的比值升高。本研究结果表明，替米沙坦通过抑制细胞凋亡反应来保护细胞免受氧化损伤。
