Shenxian Shengmai Oral Liquid Activates Nrf2/HO-1 Pathway To Inhibit Endoplasmic Reticulum Stress And Improve Sinus Node Fibrosis In SSS Mice

Purpose : To explore the regulatory mechanism of Nrf2/ ho-1 pathway in shenxian shengmai oral liquid to inhibit endoplasmic reticulum stress and improve SSS mice sinus node fibrosis,so as to provide experimental theoretical basis for the prevention and treatment of SSS by TCM compound.Material and method:Fifty SPF C57B6 mice were randomly divided into 5 groups:sham operation group(Sham group),sinus node syndrome group(SSS group),sinus node syndrome + Shenxian Shengmai treatment low-dose group(SXSM-L group),sinus node syndrome + Shenxian Shengmai treatment medium-dose group(SXSM-M group),sinus node syndrome + Shenxian Shengmai treatment of high-dose group(SXSM-H group),subcutaneous microosmosis Pumped Ang II method to establish SSS mouse model,biological information collection system collected different groups of mice at different time snack rate(1d,7d,14 d,21d,28d),HE and Masson staining to observe pathological changes,ELISA to detect oxidative stress Response markers,immunofluorescence to detect changes in ROS in oxidative stress,RT-q PCR and Western blot to detect changes in ER stress-related proteins and Nrf2 / HO-1 signaling pathway proteinsResults:1.Heart rate: Shenxian Shengmai oral solution can significantly increase the heart rate of SSS mice(P<0.05),and it is positively correlated with the concentration.2.Histology: The Shenxian Shengmai high-dose group can significantly improve tissue damage and inhibit fibrosis in the SAN area of SSS mice(P<0.05),and the improvement is positively correlated with concentration.3.Oxidative stress markers: Shenxian Shengmai Oral Liquid can inhibit the expression of MDA in the serum of SSS mice,promote the expression of SOD and CAT(P<0.05),and the regulation effect is positively correlated with the concentration.4.Endoplasmic reticulum stress-related proteins: Shenxian Shengmai Oral Liquid can significantly increase the expression of SERCA2 a and GRP78 in the SAN region of SSS mice,and down-regulate the expression of caspase-12(P<0.05).The regulation effect is positively correlated with the concentration.5.Nrf2 / HO-1 signaling pathway: Shenxian Shengmai Oral Liquid can significantly increase the expression of HO-1,Nrf2,Trx-1 in the ASN region of SSS mice(P<0.05).The regulation effect is positively correlated with the concentration.Conclusion:1.Shenxian Shengmai Oral Liquid can inhibit the damage of sinoatrial node cells by oxidative stress,thereby improving the sinus node dysfunction in SSS mice.2.Shenxian Shengmai Oral Liquid can inhibit the endoplasmic reticulum stress response of sinoatrial node cells,balance the intracellular Ca2 + homeostasis environment,maintain the autonomous rhythm of sinus node cells,and inhibit sinus node fibrosis.?3.Shenxian Shengmai Oral Liquid activates Nrf2 / HO-1 pathway to inhibit endoplasmic reticulum stress and improve sinus node fibrosis in SSS mice...