Therapeutic Effect Of Kummerowia Striata (KS) On IgA Nephropathy And Its Mechanisms

Objective:Observe the effect of Kummerowia Striata from Denglao experience prescription on the expression of platelet-derived growth factor (PDGF-B) and its mRNA in IgA nephropathy model mouse. Determine the serum level of SCR,BUN,NO in IgA nephropathy model mice. Study the Kummerowia Striata's treatment on IgA nephropathy and the IgA nephropathy mechanism of pathogenesis. Besides, explore the pharmacodynamics of Kummerowia Striata treatment on IgAN and observe its effect on the immune system,blood pressure,blood function and gastrointestinal function etc. Provide experimental foundation for the clinical treatment of IgAN and promote the research level of traditional Chinese medicine in the nephritis research area. Advance the treatment of low toxicity and efficient of traditional Chinese medicine and provide a new method of treatment.Method:The extraction conditions were optimized by orthogonal test method. Investigated by orthogonal test method and level of different factors on the extraction rate, Preparation of this selection process with the Kummerowia Striata extract as the experimental drugs tested.Using bovine serum albumin (BSA) and staphylococcal enterotoxin B (SEB) replicate IgA nephropathy mouse model. Observe the general situation of mice, serum SCR, BUN, NO level; determinate the expression of PDGF-B, PDGFR-B mRNA in IgA nephropathy mouse renal cortex by Semi-quantitative RT-PCR. Study the renal histopathology of Kummerowia Striata's treatment on IgA nephropathy model mice.Effect of Kummerowia Striata on the immune system in normal mice was used by carbon clearance method. To study its effects on blood pressure by slide method. Study trefoil clotting and bleeding time and its platelet aggregation and other hemostatic factor by capillary method. Study the effects on gastrointestinal function to promote its treatment on IgA nephropathy pharmacodynamic by semi-solid method.Results:(1) pharmacological effects of Kummerowia Striata on IgA nephropathy model mice and its mechanismAs the Kummerowia Striata effect on IgA nephropathy model mice, the living conditions of mice significantly improved while proteinuria and the amout of hematuria reduced. The content serum of SCR, BUN decreased and the whole blood NO activity (P<0.05) increased in the high dose group(12.34 g/kg).The expression of mice renal cortex PDGF-B,PDGFR-B mRNA also reduced in the high dose group. Agarose gel eletrophoresis of products from PDGF-B,PDGFR-B mRNA gene RT-PCR of IgAN model mice showed that:193bp in each group were observed at the expression of PDGF-B mRNA,the other groups gradually darkened strip compared with model group. Semi-quantitative analysis showed that the expression of PDGF-B mRNA decreased 26.8% in KS high dose group with significant differences (P<0.05) compared with model group; 203bp in each group were observed at the expression of PDGFR-B mRNA, the other groups gradually darkened strip compared with model group. Semi-quantitative analysis showed that the expression of PDGF-B mRNA decreased 18.5% in KS high dose group with significant differences(P<0.05) compared with model group.(2) Effect of Kummerowia Striata on IgA nephropathy model mice and its pharmacodynamics researchThe mice peritoneal macrophage phagocytic clearance capacity and speed were significantly increased(P<0.01) in KS high dose group (12.34 g/kg) and medium dose group (6.17g/kg). The spleen of mice were significantly improved in KS high dose group and medium dose group. KS high dose could increase the normal mouse peritoneal macrophage phagocytosis (P<0.01). KS high,medium and low dose might have an effect on the rats blood pressure decreasing but have no significant difference compared with the former administration. KS high and medium dose could significantly shorten clotting time (slide method, capillary method) (P<0.01); KS high dose group mice have significantly effect of shorten the bleeding time (P<0.01) and increase platelet count (PLT) (P<0.01). But on the red blood cell count (RBC), hemoglobin (HGB), hematocrit (HCT) have no obvious indicators of the role of trend. KS high dose could significantly promote gastric emptying (P<0.01) and intestinal propulsiving (P<0.01).(3)The best extraction of orthogonal filtering out KS:Water as extraction solvent,16 times the ratio of solid to liquid, boiling 0.5h, extract 3 times.Conclusion:KS could reduce proteinuria and the amout of hematuria in IgAN model mice, lower serum content of BUN, SCR and heal the symptoms of IgAN; significantly increase NO activity and reduce the renal cortex expression of PDGF-B and PDGFR-B mRNA in IgAN model mice;reduce the development of renal disease which is due to PDGF-B and its receptor stimulation sustained progressively over-expression of mesangial cell proliferation and matrix accumulation. KS also can enhance immunization, blood pressure, bleeding, promote gastrointestinal function. The protective effect of KS on IgAN model mice could be interrelated with the expression of PDGF-B and PDGFR-B mRNA that they might play an important role in IgAN and that may be one of the mechanisms of KS effect on IgAN.