| Objective: To study the effect of flavonoid of rosa roxburghii Tratt on the hemorheology,structural and functional changes of heart and kidney,and the reaction of cardiac endoplasmic reticulum to stress on a rat model of chronic cardiorenal syndrome.Methods: A rat model of chronic cardiorenal syndrome was established by 5/6 nephrotomy.Rats were randomly divided into sham,model and treatment groups respectively.Distilled water was given to sham and control groups,and flavoniod of rosa roxburghii Tratt(100 mg/kg bw)was given to experiment group once daily through gavage feedings at the 5th week post-nephrotomy for a total of 5 weeks respectively.Rats were anesthetized,and cardiac function was evaluated by cardiac echocardiography.Hemorheology,renal function,SOD and MDA were evaluated using blood taken from abdominal aorta.Rats were then killed by cervical dislocation,heart and kidney were fix in neutral formalin.Tissues were sectioned,and the histopathological changes were evaluated by HE staining,and the endoplasmic reticulum stress was evaluated by detecting the expression of stress markers,CHOP and GRP78 using immunohistochemistry.Results:(1)there were no significant changes in IVSd,IVSS),LVPWd,and LVIDs among groups;there was significantly increased LVIDd(P<0.05)in the model group compared to the sham group;there was significantly decreased LVPWd(P<0.01)in treatment compared to model group;and there were no significant difference(P>0.05)in other morphological indexes among groups.Compared to sham group,EF and FS were significantly decreased(P<0.01)in model group,whereas EF(P<0.01)and FS(P<0.05)were significantly increased in the treatment group when compared to the model group.(2)renofunctional indexes: compared to sham group,serum creatine and BUN were significantly increased in the model group;and when compared to the model group,BUN showed somewhat decrease but not statistically significant,whereas serum creatine showed significant decrease(P<0.05)in the treatment group.(3)HE staining: compared to the sham group,kidneys in the model group showed atrophy of most glomeruli,fibrosis,narrowing of renal capsule,hypertrophy of few glomeruli,shrinkage and shedding of some tubular epithelial cells,irregularity and dilatation of some lumen,significantly increased amount of connective tissue in the renal interstitium,and significant infilitration of inflammatory cells.Compared to the model group,kidneys in the treatment group showed less severe pathological changes in terms of atrophy of glomeruli,fibrosis,and dilatation of tubular lumen;and few atrophied and shedding of tubular epithelial cells.Compared to the sham group,cardiomyocytes are thicker and irregularly arranged,and intercalated disks become less clear in model group,and these pathological changes become less severe in the treatment group compared to the model group.(4)Changes of Hemorheology: compared to the sham group,whole blood BVH,BVM and BVL are significantly increased(P<0.01),so is the serum viscosity(P<0.05)in the model group;compared to the model group,whole blood BVH,BVM,and BVL decreased significantly(P<0.05),and PV showed somewhat decrease but not significantly different(P>0.05)in the treatment group;there were no difference observed in Hct among groups.Compared to the sham group,whole blood RV,EAI,ERI,and EEI increased significantly(P<0.01)in the model group;when compared to the model group,whole blood RV,EAI,ERI,and EEI in the treatment group were significantly decreased(P<0.05).(5)Analysis of serum SOD and MDA: the activity of SOD in the model group was significantly decreased(P<0.05)compared to the sham group,and it was significantly increased(P<0.01)in the treatment group when compared to the model group;serum MDA was significantly increased in the model group compared to the sham group(P<0.05),and it was significantly decreased in the treatment group(P<0.05)compared to the model group.(6)Immunohistochemistry evaluation: there was increased expression of CHOP and GRP78 in the kidney and heart in the model group,barely detectable in the sham group,and decreased expression in the treatment group compared to the model group.Conclusions: A rat model of chronic renocardiac syndrome was successfully established by 5/6 nephrotomy;and flavonoid of rosa roxburghii Tratt showed cardiorenal protective effect in the chronic renocardiac syndrome syndrome model rats,which may be attributed to its increased capability on anti-oxidation,its favorable effect on hemorheology,and its dampening effect on the exaggerated reaction to stress. |
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