Therapeutical Effects Of Shenhua Tablet On Experimental Chronic Nephritis And Its Stat3 Signaling Mechanism Study

Objectives: This study was to observe the therapeutic effect of a traditional Chinese drug Shenhua Tablet and to probe the mechanisms of its effects. Since the success rate of traditional chronic serum sickness in rat is low and thus difficult to be used in therapeutic effects observing, we firstly improved its founding methods, and then used it to observe the effect of Shenhua Tablet compared with Fosinopril. The main pathology change in chronic serum sickness is immunocomplex deposition and imrnflammatory cell infiltration, and Stat3 singaling is an important pathway for cytokines, so StatS may be activated in this model. We studied the StatS activation in these rats and so to explain part of the mechanisms of the effect of Shenhua.Methods: The traditional method of chronic serum sickness was modified by adding followings: one kidney removed, intraperitoneal inject LPS etc., and the effect of Shenhua Tablet on 24h proteinuria, blood biochemical indices, kidney function, pathology and immunofluorescence changes was observed compared with Fosinopril, and and the effect of Shenhua Tablet on the ED-1 positive cell number in the glomerulus, protein and mRNA expression and activation of Stat3 and protein and mRNA expression of TIMP-1 in the kidney tissue, and a-SMA positive mesangial cells were observed compared with Fosinopril using western blot, northern blot and immunohistochemistry methods.Results: Compared with that of normal control group, the model groupsshowed heavy proteinuria, lowered blood albumin, hyperlipemia, lowered kidney function, and the pathology inspection observed the proliferation of mesangial cell, infiltration of inflammatory cells, large amount of protein cast etc., and the immunofluorescence showed deposition of IgG, and C3 in the mesangial area. However, the improved method group was more serious than that of traditional method group. Shenhua Tablet significantly decreased kidney weight index, decreased urine protein, reduced serum urea nitrogen, total cholesterol, and triglyceride, increased serum albumin, total protein, improved the renal function, pathological changes and immunocomplex deposits. The ED-1 positive cell number increased, the mRNA and protein expression of Stat3 was increased and activated, protein and mRNA expression of TIMP-1, a-SMA expression was increased in the kidney tissue of rats in the model group, while in Shenhua group these up expressions and activation were decreased.Conclusion: Through the described methods we successfully established a kind of chronic serum sickness glomerulonephritis with lowered difficulty and enhanced disease rate. Shenhua Tablet is effective in treating this modified rat chronic serum sickness glomerulonephrits. It can reduce the expression and activation of Stat3 in kidney tissue of chronic serum sickness glomerulonephrits rats, which might be one of the mechanisms of its effectiveness in treating nephritis.