Regulation of N-Butanol Fraction of Gualou Xiebai Decoction on Endoplasmic Reticulum Stress in Rats with Type Ⅱ Cardiorenal Syndrome
Objective:To observe the effect of Gualou Xiebai Decoction(GXD)n-butanol fraction on endoplasmic reticulum stress in rats with type Ⅱ cardiorenal 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 type Ⅱ cardio-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 type Ⅰ and Ⅲ in the heart and kidney tissue.The endoplasmic reticulum related proteins ATF-6,GRP78,XBP-1s,ATF-4,p-eIF2α and 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 type Ⅰ and Ⅲ collagen in the heart and kidney of the model group was significantly higher than that of the sham group,while that of GXD high-dose and low-dose groups was significantly lower than that of the model group(P<0.01).The expressions of the endoplasmic reticulum-related proteins ATF-6,GRP78,XBP-1s,ATF-4,p-eIF2α and CHOP were significantly lower in the GXD group than those in the model group.Conclusion:Gualou Xiebai Decoction has obvious protective effects on the heart and kidney of type Ⅱ cardiorenal syndrome rats,and this effect may be related to the inhibition of endoplasmic reticulum stress.