瓜蒌薤白汤正丁醇部位对Ⅱ型心肾综合征大鼠内质网应激的调控作用  

Regulation of N-Butanol Fraction of Gualou Xiebai Decoction on Endoplasmic Reticulum Stress in Rats with TypeⅡCardiorenal Syndrome

作　　者：刘阳阳 张云云 李洁[1,2] 丁永芳[1,2] 彭蕴茹[1,2] LIU Yangyang;ZHANG Yunyun;LI Jie;DING Yongfang;PENG Yunru(Hospital of Integrative Chinese and Western Medicine Affiliated to Nanjing University of Chinese Medicine,Nanjing 210028,China;Jiangsu Province Academy of Traditional Chinese Medicine,Nanjing 210028,China)

机构地区：[1]南京中医药大学附属中西医结合医院,江苏南京210028 [2]江苏省中医药研究院,江苏南京210028

出　　处：《中医药信息》2024年第2期26-32,共7页Information on Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81973812);江苏省卫生健康委科研项目(M2020050)。

摘　　要：目的:观察瓜蒌薤白汤(Gualou Xiebai Decoction,GXD)正丁醇部位对Ⅱ型心肾综合征大鼠内质网应激的影响,探讨瓜蒌薤白汤对心脏和肾脏的保护作用。方法:32只SPF级健康雄性Wistar大鼠随机分为假手术组、模型组和瓜蒌薤白汤高、低剂量组。除假手术组外,其余各组采用结扎左冠状动脉前降支的方法复制Ⅱ型心肾综合征大鼠模型,灌胃给予相应药物10周后,ELISA法检测血清中NT-proBNP、Cys-C的含量;取心脏、肾脏组织,HE染色观察心脏、肾脏的细胞形态学变化,Masson染色检测组织胶原沉积和纤维化程度;透射电镜观察内质网超微结构;RT-PCR检测心、肾组织Ⅰ、Ⅲ型胶原含量;Western blot检测内质网相关蛋白ATF-6、GRP78、XBP-1s、ATF-4、p-eIF2α、CHOP的表达。结果:与假手术组比较,模型组大鼠血清中NT-proBNP、Cys-C的水平明显升高(P<0.01),瓜蒌薤白汤高、低剂量组较模型组明显降低(P<0.01)。与模型组比较,瓜蒌薤白汤组能显著改善由慢性心衰引起的大鼠心脏、肾脏组织病理学改变;透射电镜观察发现,模型组大鼠内质网肿胀、断裂,核糖体脱落,瓜蒌薤白汤组心脏、肾脏内质网基本恢复正常。RT-PCR结果表明,模型组心脏、肾脏中Ⅰ、Ⅲ型胶原mRNA表达明显高于假手术组,瓜蒌薤白汤高、低剂量组明显低于模型组(P<0.01);瓜蒌薤白汤组内质网相关蛋白ATF-6、GRP78-、XBP-1s、ATF-4、p-eIF2α、CHOP的表达显著低于模型组(P<0.01)。结论:瓜蒌薤白汤对Ⅱ型心肾综合征大鼠心脏、肾脏具有明显的保护作用,且该作用可能与抑制内质网应激有关。Objective:To observe the effect of Gualou Xiebai Decoction(GXD)n-butanol fraction on endoplasmic reticulum stress in rats with typeⅡcardiorenal syndrome,and explore the protective effects of GXD on the heart and kidneys.Methods:Thirty-two healthy male Wistar rats with SPF grade were randomly divided into sham operation group,model group,GXD high-dose and low-dose groups.Except the sham operation group,the other groups were treated with ligation of the anterior descending branch of the left coronary artery to produce the rat model of typeⅡcardio-renal syndrome.The contents of NT-proBNP and Cys-C in serum were detected by ELISA after 10 weeks of administration of the corresponding drugs.Heart and kidney tissues were taken,and cellular morphological changes in the heart and kidneys were observed with HE staining,and collagen deposition and fibrosis degree were detected with Masson staining.The ultrastructure of the endoplasmic reticulum was observed by transmission electron microscopy.RT-PCR was used to determine the levels of collagen typeⅠandⅢin the heart and kidney tissue.The endoplasmic reticulum related proteins ATF-6,GRP78,XBP-1s,ATF-4,p-eIF2αand CHOP were detected by Western blot.Results:Compared with the sham surgery group,the levels of NT-proBNP and Cys-C in the serum of rats in the model group significantly increased(P<0.01),and the levels of NT-proBNP and Cys-C in the groups of GXD were significantly lower than those in the model group(P<0.01).Compared with the model group,the GXD groups could significantly improve the pathology in the heart and kidney tissues of rats with chronic heart failure.The transmission electron microscopy showed that the endoplasmic reticulum of the model group rats was swollen,broken,and ribosome fell off,and the endoplasmic reticulum of the GXD group basically returned to normal.The RT-PCR results showed that the mRNA expression of typeⅠandⅢcollagen in the heart and kidney of the model group was significantly higher than that of the sham group,while that of GXD hig

关 键 词：瓜蒌薤白汤 Ⅱ型心肾综合征 内质网应激 

分 类 号：R285.5[医药卫生—中药学]