Study On The Mechanism Of Jianpi Qinghua Recipe Regulating TGF-?1/p38MAPK Pathway To Improve Renal Fibrosis In Rats With Unilateral Ureteral Obstruction

Objective: to investigate the model of unilateral ureteral obstruction pathological changes of renal fibrosis in rats by animal experiment reseach,and explore jianpi qinghua decoction to reduce model of unilateral ureteral obstruction rat renal fibrosis of chronic kidney disease and to delay the pathological process of chronic kidney disease by adjusting TGF-?1/p38 MAPK pathway,so as to provide relevant theoretical and experimental basis for the clinical treatment chronic kidney disease(CKD).Methods: 1.Establishment of unilateral ureteral obstruction model: 90 male SD rats of pathogen-free were selected in this study,rats were randomly divided into sham operation group and operation group,sham group rats only separate the left ureter with no ligation is performed,operation group rats received an operation with left ureteral obstruction below the renal pelvis.operation group rats were randomly divided into model group.losartan potassium group and jianpi qinghua decoction group,General condition and vital signs of rats were observed after operation.2.Starting administration the day after surgery: The losartan potassium group was treated with losartan potassium,and jianpi qinghua decoction group was treated with jianpi qinghua decoction,the sham operation group and the model group were given the Saline of the same volume.The gavage dose of the rats was 20 times of the dosage per kilogram of body weight of the clinical adults.General conditions and vital signs of the rats were observed and recorded daily during administration.the rats were weighed before each intragastric administration,The dosage of each rat was adjusted according to the body weight.A few rats' General conditions deteriorated and died during the process of gavage,relevant risk factors for death were recorded and analyzed.3.Rats in each group were sacrificed at 7,14 and 21 days after intragastric administration.Blood samples were obtained from abdominal aorta after treatment,Biochemical method was used to detect serum creatinine and urea nitrogen in rats.The lateral renal tissue of the model was cut open,reject the accumulated liquid.Part of the kidney was stored at room temperature in 4% paraformaldehyde solution,the pathological morphology of the kidney was observed by HE and Masson staining.The expression of p38MAPK?collagen ?,collagen ?,Fibronectin and Laminin were detected by immunohistochemical.Another part of the kidney is stored in liquid nitrogen then transferred to-80 ? refrigerator,the m RNA expression levels of Smad2 and Smad3 and TGF-?1 m RNA were detected by real-time polymerase chain reaction,the protein expression levels of p38 MAPK?p-p38 MAPK?TGF-?1?collagen ??collagen ?were demined by Western blot.Results:1.As compared with sham operation group,The content of SCr and BUN,the protein expression levels of p38 MAPK?p-p38 MAPK?TGF-?1?collagen ? and collagen ?,Fibronectin and Laminin of model group were increased significantly(P < 0.01,P < 0.05),the m RNA expression levels of Smad2 and Smad3 and TGF-?1 were higher in model group(P < 0.01,P < 0.05);2.As compared with model group,The content of SCr and BUN,the protein expression levels of p38 MAPK?p-p38 MAPK?TGF-?1?collagen ? and collagen ?,Fibronectin and Laminin of model group were decreased(P < 0.01,P < 0.05),the m RNA expression levels of Smad2 and Smad3 and TGF-?1 were lower in model group(P < 0.01,P < 0.05)in both losartan potassium group and jianpi qinghua decoction group.Conclusion: 1.Jianpi qinghua decoction can reduce the content of SCr,BUN,To some extent,renal filtration and reabsorption can be improved,relieve azotemia,delay the progressive decline of renal function in chronic kidney disease.2.Jianpi qinghua decoction can alleviate renal fibrosis by reduce the protein expression levels of p38 MAPK?p-p38 MAPK?TGF-?1?collagen ? and collagen ?,Fibronectin and Laminin,lower the m RNA expression levels of Smad2 and Smad3 and TGF-?1.