温阳振衰颗粒对心肾综合征模型大鼠血浆外泌体及心、肾组织p38MAPK表达的影响Effects of Wenyang Zhenshuai Granules (温阳振衰颗粒) on the Expression of p38MAPK in the Plasma Exosomes and the Tissues of Heart and Kidney of Cardio-Renal Syndrome Model Rats
欧阳过;蔡虎志;王雅乐;王敏;陈青扬;刘越美;陈新宇;
摘要(Abstract):
目的探讨温阳振衰颗粒对心肾综合征大鼠心功能、肾功能的影响及可能作用机制。方法 40只SD大鼠随机分为空白组、模型组、温阳振衰组、依那普利组,每组10只。除空白组外其余各组大鼠采用阿霉素3mg/kg腹腔注射,每周1次,共6周建立心肾综合征大鼠模型。造模3周后空白组和模型组大鼠给予生理盐水每次1ml/100g灌胃,温阳振衰组每次给予0.72g/kg温阳振衰颗粒灌胃,依那普利组每次给予0.9mg/kg依那普利片灌胃。每天给药2次,连续4周。HE染色观察肾组织病理改变,TUNEL法检测心肌及肾组织细胞凋亡阳性率,检测心功能、肾功能及血清N端前脑钠素(NT-pro BNP)、肾损伤分子1(KIM-1)含量,检测心脏和肾脏p38丝裂原活化蛋白激酶(p38MAPK)和磷酸化p38丝裂原活化蛋白激酶(p-p38MAPK)蛋白及mRNA表达,检测血浆外泌体定量,心脏、肾脏组织及血浆外泌体miR-155表达。结果与空白组比较,模型组大鼠心功能、肾功能损伤,心肌及肾组织细胞凋亡阳性率增加,血清NT-pro BNP、KIM-1含量升高,心脏和肾脏p-p38MAPK蛋白、p38MAPK mRNA表达均升高,心脏、肾脏和血浆外泌体miR-155均降低(P<0.05或P<0.01);与模型组比较,温阳振衰组和依那普利组上述指标均不同程度改善(P<0.01)。结论温阳振衰颗粒可改善心肾综合征模型大鼠心功能、肾功能,其作用可能与增加外泌体miR-155抑制p-p38MAPK表达,从而抗细胞凋亡有关。
关键词(KeyWords): 心肾综合征;温阳振衰颗粒;外泌体;miR-155;p38丝裂原活化蛋白激酶;细胞凋亡
基金项目(Foundation): 国家自然科学基金(81704061; 81173213);; 湖南省自然科学基金(2019JJ50465);; 湖南省教育厅科学研究项目(18A218);; 湖南省中医药科研计划项目(201904);; 湖南中医药大学研究生创新课题(2018CX11);湖南中医药大学中医学国内一流建设学科
作者(Author): 欧阳过;蔡虎志;王雅乐;王敏;陈青扬;刘越美;陈新宇;
Email:
DOI: 10.13288/j.11-2166/r.2020.15.014
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