替米沙坦对高浓度葡萄糖引起的内皮细胞间质化的影响

Effect of telmisartan on endothelial-mesenchymal transition induced by high-concentration glucose

目的探讨替米沙坦对高浓度葡萄糖引起的内皮细胞间质化的影响。方法采用体外分离培养的人脐静脉内皮细胞(HUVEC)作为细胞模型,通过高浓度葡萄糖(30 mmol/L)诱导内皮细胞间质化,TGF-β抑制剂SB-431542或替米沙坦预处理内皮细胞6 h,然后用高浓度葡萄糖(30 mmol/L)孵育脐静脉内皮细胞48 h。RT-PCR和Western blot观察CD31、VE-cadherin、α-SMA和Vimentin表达变化。应用糖尿病小鼠模型验证上述指标的变化。结果高浓度葡萄糖可以促进内皮细胞TGF-β的表达,而替米沙坦可抑制高浓度葡萄糖引起的TGF-β表达增加;高浓度葡萄糖可以降低内皮细胞CD31、VE-cadherin的表达,增加α-SMA及Vimentin的表达。TGF-β抑制剂SB-431542及替米沙坦可以显著逆转高浓度葡萄糖对内皮细胞间质化的影响。结论替米沙坦可以降低TGF-β的表达,抑制高浓度葡萄糖诱导的内皮细胞间质化。

Objective To investigate the effect of telmisartan on endothelial-mesenchymal transition induced by high-concentration glucose. Methods Endothelial cells were isolated from human umbilical vein endothelial cells （HUVECs）. High-concentration glucose （30 mmol/L） was used to induce the endothelial-mesenchymal transition. The endothelial cells were pretreated by TGF-β inhibitor SB-431542 （5 μmoL/L） or telmisartan （5 mmol/L） for 6 h,and were co-cultured with high-concentration glucose （30 mmol/L） for 48 h. The changes of CD31, VE-cadherin, α-SMA and vimentin were determined by RT-PCR and Western blot. Diabetic mice model was used to verify the changes of the above indicators. Results High-concentration glucose could increase the expression of TGF-β, which could be reversed by telmisartan. High-concentration glucose could decrease the expression of CD31 and VE-cadlaerin, and increase the expression of a-SMA and vimentin. TGF-β inhibitor SB-431542 and telmisartan could significantly reverse the effects of high-concentration glucose on endothelial-mesenchymal transition. Conclusion Telmisartan can reduce the expres- sion of TGF-β, and inhibit the endothelial-mesenchymal transition induced by high-concentration glucose.