Protective effects of cryptotanshinone on heart and kidney function in rats with cardiorenal syndrome by regulating PI3K/Akt/mTOR signaling pathway
- VernacularTitle:隐丹参酮调节PI3K/Akt/mTOR信号通路对心肾综合征大鼠心肾功能的保护作用
- Author:
Xin WANG
1
;
Hua LU
1
;
Lujiao KONG
1
;
Xiaoyang GUO
1
;
Tingting MA
1
;
Yue LU
1
Author Information
1. Dept. of Nephrology，Xingtai People’s Hospital，Hebei Xingtai 054000，China
- Publication Type:Journal Article
- Keywords:
cryptotanshinone;
PI3K/Akt/mTOR signaling pathway;
cardiorenal syndrome;
heart and kidney function
- From:
China Pharmacy
2024;35(17):2096-2101
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the protective effect and mechanism of cryptotanshinone （CTS） on heart and kidney function in rats with cardiorenal syndrome （CRS） by regulating phosphoinositide kinase-3 （PI3K）/protein kinase B （Akt）/ mammalian target of rapamycin （mTOR） signaling pathway. METHODS CRS model of rats was induced by left anterior descending coronary artery ligation combined with acute renal ischemia-reperfusion injury. Model rats were randomly divided into CRS model group （CRS group）， low-dose CTS group （CTS-L）， high-dose CTS group （CTS-H group）， high-dose CTS+PI3K activator 740Y-P group （CTS-H+740Y-P group）， with 12 rats in each group. Another 12 rats were selected as the normal control group （Normal group） and were carried out surgery without modeling. CTS-L group and CTS-H group were respectively given CTS 30 and 60 mg/kg intragastrically， once a day， for consecutive 14 d. Besides the intervention of CTS 60 mg/kg intragastrically， CTS-H+740Y-P group was given 10 mg/kg 740Y-P intraperitoneally， once a day， for 14 consecutive days. After the last medication， the levels of cardiac function [left ventricular ejection fraction （LVEF）， left ventricular end-systolic diameter （LVESD）， left ventricular end-diastolic diameter （LVEDD）， left ventricular fraction shortening （LVFS）] and renal function [24 h urinary protein， blood urea nitrogen （BUN）， serum creatinine （Scr）， brain natriuretic peptide （BNP）] were detected in rats. The pathological changes and fibrosis of the heart and kidney in rats were observed； the expressions of PI3K/Akt/mTOR signaling pathway in heart and renal tissue were all detected. RESULTS Compared with Normal group， the levels of LVEF and LVFS in rats were all decreased significantly in CRS group （P＜0.05）； the levels of LVESD， LVEDD， 24 h urinary protein， serum levels of BUN， Scr and BNP， collagen area and the phosphorylation of PI3K， Akt and mTOR protein in heart and renal tissue were all increased significantly （P＜0.05）. The morphology of myocardial cells was enlarged and disordered； the structure ofrenal tubules was disordered， epithelial cells were wrinkled， and there was infiltration of inflammatory cells. Compared with CRS group， the above indexes of rats were reversed significantly in CTS-L group and CTS-H group （P＜0.05）； heart and kidney function had been restored， and pathological damage and fibrosis had been reduced. PI3K activator 740Y-P weakened the protective effect of CTS on cardiac and renal function in CRS rats. CONCLUSIONS CTS can protect heart and kidney function in CRS rats， the mechanism of which may be associated with inhibiting the PI3K/Akt/mTOR signaling pathway.
