Tu Rong-Fang, He Zhen-Hua, Tan Xiao-Wu, Chen Zhe, Zeng Sai-Li, Liu Sha, Jia Yuan-Hang, Li Xue-Hua
The Second Affiliated Hospital, Department of Pulmonary and Critical Care Medicine, Hengyang Medical School, University of South China, Hengyang 421001, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2021 Sep;37(5):454-459. doi: 10.12047/j.cjap.6120.2021.068.
To investigate the effects of simvastatin (SIM) on pulmonary fibrosis and the expression of VE-cadherin(VE-cad),vimentin(VIM) and alpha-smooth muscle actin(α-SMA)in the pulmonary fibrosis tissue of rats. Sixty healthy male SD rats were randomly divided into control group(group A), bleomycin group(group B), 5 mg SIM group (group C) and 10 mg SIM group (group D),15 rats in each group. The model of rat pulmonary fibrosis was established by itraperitoneal injection of bleomycin(5 mg/kg). Since the first day of modeling, the rats of group C and D were treated with simvastatin suspension 5 mg/(kg·d) and 10 mg/(kg·d) by intragastric administration everyday, and the rats of group A and B were treated with equal volume of saline 10 ml/(kg·d) everyday. Five rats of each group were sacrificed randomly at the 7th, 14th and 28th day. Masson staining was used to observe the morphological changes of lung tissue in rats. The degree of fibrosis in lung tissues of each group was evaluated by the content of hydroxyproline (HYP) . The microvessel density (MVD) was analyzed by immunohistochemistry,The expressions of protein and mRNA of VE-cad, VIM and α-SMA were determined by immunohistochemistry and RT-PCR. ①Compared with group A, the levels of HYP and MVD, the mRNA and protein expression levels of VIM and α-SMA in lung tissues of groups B, C and D were increased significantly at the 7th, 14th and 28th day(all ＜0.05), which reached highest level at the 28th day. However, the mRNA and protein expression levels of VE-CAD were decreased significantly at the corresponding time (＜0.05), which reached lowest level at 28th day. ②Compared with group B, the levels of HYP and MVD, the mRNA and protein expression levels of VIM and α-SMA in groups C and D were decreased at the 7th, 14th and 28th day (all ＜0.05), which were decreased more obviously in group D at the 28th day. However, the mRNA and protein expression levels of VE-CAD were increased at the corresponding time (all ＜0.05), which were increased more obviously in group D at the 28th day. Simvastatin can reduce the degree of pulmonary fibrosis in rats through inhibiting the process of EnMT, which can enhance the expression of VE-cad and reduce the expression of VIM and α-SMA.
探讨辛伐他汀（SIM）对大鼠肺纤维化及肺纤维化组织中血管内皮钙黏蛋白（VE-cad）、波形蛋白（VIM）和α-平滑肌肌动蛋白（α-SMA）表达的影响。将60只健康雄性SD大鼠随机分为对照组（A组）、博来霉素组（B组）、5mg SIM组（C组）和10mg SIM组（D组），每组15只。采用腹腔注射博来霉素（5mg/kg）建立大鼠肺纤维化模型。自建模第1天起，C组和D组大鼠每天经胃内给予辛伐他汀混悬液5mg/（kg·d）和10mg/（kg·d），A组和B组大鼠每天给予等体积生理盐水10ml/（kg·d）。每组于第7、14和28天随机处死5只大鼠。采用Masson染色观察大鼠肺组织形态学变化。通过羟脯氨酸（HYP）含量评估各组肺组织纤维化程度。采用免疫组织化学分析微血管密度（MVD），采用免疫组织化学和RT-PCR检测VE-cad、VIM和α-SMA的蛋白及mRNA表达。①与A组比较，B组、C组和D组大鼠肺组织在第7、14和28天HYP和MVD水平、VIM和α-SMA的mRNA及蛋白表达水平均显著升高（均P＜0.05），在第28天达到最高水平。而相应时间VE-CAD的mRNA及蛋白表达水平显著降低（P＜0.05），在第28天达到最低水平。②与B组比较，C组和D组大鼠在第7、14和28天HYP和MVD水平、VIM和α-SMA的mRNA及蛋白表达水平均降低（均P＜0.05），第28天D组降低更明显。而相应时间VE-CAD的mRNA及蛋白表达水平升高（均P＜0.05），第28天D组升高更明显。辛伐他汀可通过抑制上皮-间质转化过程减轻大鼠肺纤维化程度，该过程可增强VE-cad表达并降低VIM和α-SMA表达。
