摘要
目的探究红景天苷对ApoE(-/-)小鼠动脉粥样硬化的影响及所涉及的相关分子机制。方法将ApoE(-/-)小鼠分为正常饮食组(ND组),高脂肪饮食组(HFD组),AMPK激活剂组(AC组),低(L-SAL组)、高(H-SAL组)剂量红景天苷组。应用苏丹Ⅳ染色、HE染色和Masson染色行ApoE(-/-)小鼠动脉粥样硬化病变分析;应用主动脉内皮依赖性舒张功能实验检测Apo E(-/-)小鼠主动脉血管内皮舒张功能;应用免疫组织化学分析主动脉p-AMPK、p-PI3K、p-Akt、p-e NOS蛋白表达情况;应用蛋白免疫印迹分析ApoE(-/-)小鼠AMPK、PI3K、Akt、eNOS蛋白磷酸化水平。结果与ND组小鼠相比,HFD组病变区面积、斑块面积均显著增加,而胶原含量显著降低(P<0.05)。与HFD组相比,L-SAL组和H-SAL组病变区面积、斑块面积均显著降低(P<0.05),胶原含量显著增加(P<0.05),且H-SAL组与L-SAL组差异有统计学意义(P<0.05)。与ND组相比,HFD组内皮依赖性舒张功能显著降低(P<0.05)。与HFD组相比,L-SAL组和H-SAL组内皮依赖性舒张功能均显著增加(P<0.05)。与ND组相比,HFD组p-AMPKα(Thr172)、p-PI3K、p-Akt、p-eNOS(Ser1177)MOD值均显著降低(P<0.05)。与HFD组相比,AC组、L-SAL组和H-SAL组p-AMPKα(Thr172)、p-PI3K、p-Akt、p-eNOS(Ser1177)MOD值均显著增加(P<0.05)。与ND组相比,HFD组p-AMPKα(Thr172)、p-PI3K、p-Akt、p-eNOS(Ser1177)蛋白表达显著降低(P<0.05)。与HFD组相比,L-SAL组和H-SAL组p-AMPKα(Thr172)、p-PI3K、p-Akt、p-eNOS(Ser1177)蛋白表达显著增加(P<0.05)。H-SAL组与AC组各项指标相比差异无统计学意义(P>0.05)。结论红景天苷能够通过激活AMPK/PI3K/Akt/e NOS信号级联,改善与e NOS活化相关的血管内皮功能,从而减轻Apo E(-/-)小鼠动脉粥样硬化病变。
Objective To investigate the effect of salidroside on atherosclerosis in Apo E（-/-） mice and the related molecular mechanisms. Methods Apo E（-/-） mice were divided into normal diet group（ ND group）,and high fat diet group（ HFD group）,AMPK activator group（ AC group）,low（ L-SAL group）,and high（ H-SAL Group） dose of salidroside group. The pathological analysis of atherosclerotic lesions in Apo E（-/-） mice was assessed by Sudan Ⅳ staining,HE staining and Masson staining. The endothelium-dependent vasodilatation function of Apo E（-/-） mice was detected by endothelium-dependent diastolic function test. The expression of p-AMPK,p-PI3 K,p-Akt and p-e NOS protein in aorta was analyzed by immunohistochemistry. The phosphorylation of AMPK,PI3 K,Akt and e NOS protein in Apo E（-/-）mice was analyzed by Western blot. Results Compared with ND group,the lesion area and plaque area of HFD group were significantly increased,while the content of collagen was significantly decreased（ P〈0. 05）. Compared with HFD group,the lesion area and plaque area of L-SAL group and H-SAL group were significantly decreased（ P〈0. 05）,and there were significant differences between H-SAL group and L-SAL group（ P〈0. 05）. Compared with ND group,the endothelium-dependent diastolic function was significantly decreased in HFD group（ P〈0. 05）. Compared with HFD group,the endothelium-dependent diastolic function of L-SAL group and H-SAL group was significantly increased（ P〈0. 05）. Compared with ND group,the MOD value of p-AMPKα（ Thr172）,p-PI3 K,p-Akt and p-e NOS（ Ser1177） in HFD group was significantly decreased（ P〈0. 05）. Compared with HFD group,the MOD value of p-AMPKα（ Thr172）,pPI3 K,p-Akt and p-e NOS（ Ser1177） in AC group,L-SAL group and H-SAL group was significantly increased（ P〈0. 05）. Compared with ND group,the expression of p-AMPKα（ Thr172）,p-PI3 K,p-Akt and p-e NOS（ Ser1177） protein in HFD group was decreased（ P〈0. 05）. Compared with HFD group,the expression of p-AMPKα（ Thr172）,p-PI3 K,pAkt and p-e NOS（ Ser1177） protein in L-SAL group and H-SAL group was significantly increased（ P〈0. 05）. There was no significant difference in the above indexes between H-SAL group and AC group（ P〈0. 05）. Conclusion Salidroside can attenuate the atherosclerotic lesions of Apo E（-/-） mice by activating AMPK/PI3 K/Akt/e NOS signal cascade and improving the e NOS-associated vascular endothelial function.
作者
左晓利
黄红莹
孟祥毅
ZUO Xiao-li;HUANG Hong-ying;MENG Xiang-yi(Biochemistry Teaching and Research Section, Department of Basic Medicine, Anyang Vocational and Technical College, Anyang 455000, Chin)
出处
《实用药物与临床》
CAS
2018年第5期481-486,共6页
Practical Pharmacy and Clinical Remedies
