Effect of Shuangshen Xionglian Granule on Vasodilation and PI3K/Akt/eNOS Pathway in Hyperhomocysteinemia Chronic Kidney Disease Rats
10.13422/j.cnki.syfjx.20202007
- VernacularTitle:双参芎连颗粒对高同型半胱氨酸血症慢性肾病大鼠血管舒张及PI3K/Akt/eNOS通路的影响
- Author:
Lei LI
1
;
Hong-xu MENG
1
;
Li LIN
1
;
Long JIN
1
;
Yue SHI
1
;
Yan-lei MA
1
;
Jian-xun LIU
1
Author Information
1. Beijing Key Laboratory of Chinese Materia Pharmacology， Institute of Basic Medical Sciences of Xiyuan Hospital， China Academy of Chinese Medical Sciences， Beijing 100091， China
- Publication Type:Research Article
- Keywords:
Shuangshen Xionglan granule;
hyperhomocysteine;
chronic kidney disease;
vascular disease;
phosphatidylinositol 3 kinase （PI3K）/serine threonine kinase （Akt）/nitric oxide synthase （eNOS） signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2021;27(1):88-97
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To study the effect of Shuangshen Xionglian （SSXL） granules on vasculopathy and phosphatidylinositol 3 kinase （PI3K）/serine threonine kinase （Akt）/nitrogen oxide synthase （eNOS） signal in hyperhomocysteinemia chronic kidney disease rats. Method:Rats were randomly divided into 5 groups： sham operation group， model group， and high， medium and low-dose （8， 4， 2 g·kg-1） SSXL groups. The model of hyperhomocysteinemia chronic kidney disease in rats was established with high methionine feed combined with 5/6 nephrectomy. After 5/6 nephrectomy， continuous intragastric administration lasted for four weeks. Arterial blood pressure was measured at the 4th and 8th weeks after operation. At the end of the 8th week after the operation， blood was collected to determine serum creatinine， urea nitrogen， homocysteine （Hcy）， methionine and blood lipid. Western blot was used to detect the expressions of PI3K/Akt/eNOS pathway-related proteins， such as p-p85， p-Akt and p-Ser177 in thoracic aorta， and serum NO and eNOS were measured. The changes of endothelium-dependent relaxation and non-endothelium-dependent relaxation were measured by the method of isolated thoracic aorta ring. Pathological htoxylin eosin （HE） staining was used to observe the changes of renal tissue and thoracic aorta. Result:At the 8th week of the experiment， compared with the sham operation group， arterial systolic blood pressure， serum urea nitrogen， creatinine， Hcy， methionine， total cholesterol and low-density lipoprotein of the model group were significantly increased. Four weeks later after administration， arterial systolic blood pressure， serum urea nitrogen， Hcy， methionine， serum total cholesterol and serum low-density lipoprotein were significantly reduced in each dose group （P<0.05， P<0.01）. The creatinine in the SSXL 8， 4 g·kg-1 group was significantly reduced （P<0.05）. The nitric oxide content of SSXL in each dose groups were increased compared with that in the model group （P<0.05， P<0.01）， and the serum eNOS activity of the SSXL in the SSXL 8 g·kg-1 group was significantly increased compared with that in the model group （P<0.05）. The endothelium dependent and non-endothelium dependent vasodilation of thoracic aortic rings in the model group were significantly damaged. The cumulative concentration of acetylcholine （1×10-5.5~1×10-4 mmo1·L-1） in the SSXL 8 g·kg-1 group was significantly improved （P<0.05， P<0.01）. The diastolic degree of the vascular ring in the SSXL 8 g·kg-1 group was significantly higher than that in the model group （P<0.05）. Western blot results showed that the expressions of p-85， p-Akt and p-Ser177 in blood vessels increased in the sham group compared with those in the model group （P<0.01）. Compared with the model group， the phosphorylation level of this pathway was increased in the SSXL groups， and the expressions of p-Akt and p-Ser177 in the SSXL 8 g·kg-1 group were significantly increased （P<0.05）. The pathological results showed that the pathological changes of thoracic aorta and renal tissue in the dosages of SSXL were significantly reduced compared with those in the model group. Conclusion:SSXL granules can improve hyperhomocysteine and dyslipidemia in rats of chronic kidney disease with hyperhomocysteine， reduce serum creatinine， urea nitrogen levels and arterial systolic blood pressure， and improve vascular morphology and diastolic function， which may be related to the regulation of the PI3K/Akt/eNOS signaling pathway.
