Effects Of Trimetazidine On Renal Fibrosis In Rats With Chronic Heart Failure

As the chronic wasting disease,chronic heart failure is a clinical syndrome and the end-stage of heart diseases with high morbidity and mortality. The clinical manifestations is associated with kidney, liver, lung and other organs dysfunction, especially prone to renal insufficiency. According to previous study, incidence of worsened renal function in patients with chronic heart failure is 22.7%.What is the pathology of worsening renal function in rats with heart failure?The research about that is less both at home and abroad. Trimetazidine,a myocardial metabolic drug, widely used in heart diseases, including chronic heart failure,due to its strong effect on anti- ischemia and antioxidant.This study was to explore the effects of trimetazidine on renal fibrosis in rats with chronic heart failure through the expression of platelet derived growth factor-B and connective tissue growth factor.Objective:Preparering the model rats with chronic heart failure by abdominal aorta constriction, after successful preparation of model,we can observe the structural changes in the kidney through HE staining and Masson stain method under the light microscope. To detect the expression of PDGF- B and CTGF in the kidney of each group of rats with SP immunohistochemical method and Western Blot method. To detect the expression of PDGF- B m RNA and CTGF m RNA in the kidney of each group of rats by Reverse transcriptase PCR. To explore the Effects of Trimetazidine on renal fibrosis in rats with chronic heart failure.Methods:1 There are 40 male Wistar rats on clean level were randomly divided into control group(no ligation of the abdominal aorta), heart failure model group and the trimetazidine group, 10 rats in each group.To establish the rat model with chronic heart failure by abdominal aorta coarctation. Model standard: left ventricular end-diastolic pressure(LVEDP)?15mm Hg.2 When rats in each group reach the end of observation, To detect thehemodynamic LVEDP and the maximum rate of left ventricular pressureincrease and decrease by multi-lead electric physiological record instrument.3 To observe the pathological structure changes in the kidney under thelight microscope through HE staining and Masson stain method.4 To detect the expression of PDGF- B and CTGF in the kidney in ratsby SP immunohistochemical method.5 To detect the level of expression of PDGF- B and CTGF in the kidneyin rats by Western Blot method.6 To detect the level of PDGF-B m RNA and CTGF m RNA in the kidneyin rats by Reverse transcriptase PCR.Results:1 Hemodynamic indexes of rats in each group of data:The LVEDP in the sham group, model group, trimetazidine group were(6.93±0.37)mm Hg、(17.09±0.36)mm Hg、(9.73±0.31)mm Hg;the ±dp/ in the control group, model group, trimetazidine group were(5373.69±71.63)mm Hg/s &(4309.88±136.65)mm Hg/s、(4214.49±31.06)mm Hg/s &(2844.72±56.96) mm Hg/s 、( 4809.429 ± 39.85) mm Hg/s &( 3372.63 ± 64.50)mm Hg/s. Compared with the sham group, the LVEDP significantly increased and ± dp/dtmax decreased in the model group, the difference was statistically significant( P < 0.01). Compared with the model group, the LVEDP significantly decreased and ± dp/dtmax increased in the trimetazidine group, the difference was statistically significant(P<0.01).2 The pathological changes in the kidney in each group of rats:2.1 HE staining results: In the sham group, glomerular and tubularstructure was clear, tubular epithelial cells arranged in neat rows; in themodel group,the tubule luminal were significant expansion,the dyed wasmore lighter in renal tubular epithelial cells, the arrangement of cellsbecame apparent disorder; in the trimetazidine group the lumen of renaltubules slightly expanded, staining of renal tubular epithelial cells was in alighter, the arrangement of cells became disorder;2.2 Masson staining results: In the sham group,there was not obviously collagen deposition in the renal interstitium and glomcrulus; In the model group,a great deal of collagen deposition in the renal interstitium; The trimetazidine group was seen a small amount of collagen deposition in the renal interstitium.3 The expression of PDGF- B and CTGF in the kidney in rats:3.1 SP immunohistochemical method :(1)Expression of PDGF-B:Sham group showed no positive expression,model group showed a strong positive expression in the tubular epithelialcells and renal interstitial cells; trimetazidine group was significantlyreduced.(2)Expression of CTGF: Sham group showed no positive expression,model group showed a strong positive expression in the tubular epithelialcells and renal interstitial cells; trimetazidine group was significantlyreduced.3.2 Western Blot method : Compared with the sham group, theexpression level of PDGF-B and CTGF in the kidney significantly increasedin the model group(P<0.05); The expression of PDGF-B and CTGF in thekidney in the trimetazidine group was significantly lower than the modelgroup(P<0.05).4 The m RNA level of PDGF- B m RNA and CTGF m RNA in thekidney in rats : Compared with the sham group, the m RNA level of PDGF-B and CTGF in the kidney significantly increased in the model group(P<0.05); the m RNA level of PDGF-B and CTGF in the kidney in thetrimetazidine group was significantly lower than the model group(P<0.05).Conclusion:1 Chronic heart failure can cause renal interstitial fibrosis in rats.2 Trimetazidine can effectively suppress the progress of renal interstitial fibrosis in rats with chronic heart failure.