| Objective: To explore the effects and mechanism of rosuvastatin calcium combined with metformin on renal damage in elderly patients with diabetes mellitus(type 2 diabetes mellitus,T2DM)through clinical studies and animal experiments.METHODS: Clinical studies section used case-control study,T2 DM Kidney injury patients(age ≥ 60 years)who were hospitalized in the cadre ward of the 960 th Hospital of the People’s Liberation Army from December 1,2016 to December 1,2018 were enrolled.The patients who met the syndrome of phlegm dampness and qi and yin deficiency were randomly selected,and a total of 60 patients were divided into two groups of 30 cases each.To observe the changes of serum urea nitrogen(BUN),serum creatinine(CRE),cystin protease inhibitor(Cys C)and blood lipid(LDL,low density lipoprotein)levels and changes of TCM syndrome scores in patients with phlegm-dampness syndrome and qi-yin deficiency syndrome.Forty animals of Wistar rats were raised in the animal experiment to establish T2 DM rat models.After successful modeling,the rats were randomly divided into: the blank control group,T2 DM blank control group,low-dose rosuvastatin calcium group and high-dose rosuvastatin calcium group.Low-dose rosuvastatin calcium and high-dose rosuvastatin calcium were given rosuvastatin calcium.According to the conversion formula.:The dose of rats(mg/kg)= 6.25 × human dose(mg / kg).Low dose of rosuvastatin calcium(0.42mg/kg)and High dose of rosuvastatin calcium(0.83mg/kg)combined with metformin(200mg/kg)were administered for 8 weeks.The blank control group was given an equal dose of normal saline,and the T2 DM blank control group was given an equal dose of metformin(200 mg/kg)and a 0.1%solution in physiological saline.After the end of the treatment,the blood was taken for biochemical tests,and the kidneys were examined by light microscopy,electron microscopy and immunopathology.The morphological changes of the kidneys were observed to investigate the mechanism of rosuvastatin calcium on renal injury in T2 DM rats,which provide scientific theory and experimental basis for the differentiation of traditional Chinese medicine and Western medicine for the treatment of diabetic kidney injury.Results:(1)Clinical research: 1.The rosuvastatin calcium treatment group had a good effect in improving elderly diabetic kidney injury.BUN,CRE,Cys C and LDL were all reduced,and the phlegm-dampness syndrome had more advantageous than Qi and Yin deficiency syndrome in reducing kidney damage(P<0.05).2.After the treatment of phlegm-dampness syndrome and qi-yin deficiency syndrome,the scores of TCM syndromes decreased,and the scores of TCM syndromes of phlegm-dampness syndrome decreased more significantly(P<0.05).(2)Animal experiment: BUN,CRE and Cys C were decreased after treatment with rosuvastatin calcium and metformin(P<0.05).Kidney light microscopic(LM)examination: Rosuvastatin calcium combined with metformin reduced tubular dilatation,reduced tubular inflammatory cell infiltration,and decreased tubular tubular formation.Electron microscopy: Rosuvastatin calcium combined with metformin reduced the thickening of glomerular basement membrane in diabetic rats,slowed the proliferation of mesangial cells and stromal cells,and reduced the wall thickening of renal interstitial vessels.By inhibiting the activity of HDAC enzyme,the content of Glut4 in kidney tissue is increased.Conclusion:(1)Clinical research: 1.Rosuvastatin calcium combined with metformin can reduce BUN,CRE,Cys C,LDL and protect kidney function.2.Rosuvastatin calcium combined with metformin can reduce the TCM syndrome scores of elderly patients with kidney injury.(2)Animal experiment: Rosuvastatin calcium combined with metformin can reduce the inflammatory reaction caused by glucose toxicity,and also can inhibit tubular dilatation,inhibit tubular tubular epithelial cell swelling and thinning,maintain renal tubular volume,reduce renal fibrosis,and thereby protect renal tissue. |