Huo Qianqian, Wang Ting, Wang Tao, Zhang Rui
Department of Cardiology, Jining Νo. 1 People's Hospital, Jining, Shandong 272011, P.R. China.
Department of Cardiology, Zoucheng People's Hospital, Zoucheng, Shandong 273500, P.R. China.
Exp Ther Med. 2019 Mar;17(3):2317-2321. doi: 10.3892/etm.2019.7210. Epub 2019 Jan 28.
The effect and mechanism of acetazolamide on cardiac fibrosis induced by transverse aortic constriction (TAC) were investigated. C57BL/6 mice were subjected to TAC or sham operation and then were orally gavaged with acetazolamide (20 mg/kg/day). After 4 weeks of operation, cardiac function was detected by echocardiography. Interstitial fibrosis was stained with Masson's trichrome. The expression of α-smooth muscle actin (α-SMA), collagen I, transforming growth factor-β1 (TGF-β1) and Smad2 were measured by western blotting. The TAC mice displayed significant cardiac dysfunction and fibrosis. The expression of α-SMA, collagen I, TGF-β1 and p-Smad2 in the TAC group was higher than those in the sham group. By contrast, acetazolamide administration inhibited interstitial fibrosis, as well as improved cardiac dysfunction induced by TAC. Acetazolamide also reduced the expression of α-SMA, collagen I, TGF-β1 and p-Smad2 in the TAC mice. Acetazolamide was able to attenuate cardiac fibrosis and improve cardiac dysfunction. The molecular mechanism involved in the anti-fibrotic effect of acetazolamide possibly was through inhibiting TGF-β1/Smad2 signaling pathway.
研究了乙酰唑胺对横断主动脉缩窄（TAC）诱导的心脏纤维化的作用及其机制。将C57BL/6小鼠进行TAC手术或假手术，然后口服给予乙酰唑胺（20mg/kg/天）。术后4周，通过超声心动图检测心脏功能。用Masson三色染色法检测间质纤维化。通过蛋白质免疫印迹法检测α-平滑肌肌动蛋白（α-SMA）、I型胶原、转化生长因子-β1（TGF-β1）和Smad2的表达。TAC小鼠表现出明显的心脏功能障碍和纤维化。TAC组中α-SMA、I型胶原、TGF-β1和磷酸化Smad2的表达高于假手术组。相比之下，给予乙酰唑胺可抑制间质纤维化，并改善TAC诱导的心脏功能障碍。乙酰唑胺还降低了TAC小鼠中α-SMA、I型胶原、TGF-β1和磷酸化Smad2的表达。乙酰唑胺能够减轻心脏纤维化并改善心脏功能障碍。乙酰唑胺抗纤维化作用的分子机制可能是通过抑制TGF-β1/Smad2信号通路。
