Effect Of Qingli Huoxue Yangyin Fang On The Abnormal Glycosylation Of IgA1 And Expression Of Vascular Endothelial Growth Factor And Its Receptor Flk-1 In Rats With IgA Nephropathy

ObjectiveWe observed the effect of Qingli Huoxue Yangyin Fang on the abnormal glycosylation of IgA1 and the expression of vascular endothelial growth factor(VEGF) and its receptor Flk-1 in rats with IgA nephropathy in order to explore its interventional mechanism for IgA nephropathy(IgAN).Methods1. We established IgAN rat model by adopting two modified methods, such as BSA + LPS + CCL4 and BSA + SEB + immune adjuvant + CCL4. Comparing the differences of clinical symptoms, biochemical indicators, and renal pathological changes in two rat models, we choosed the better one.2. We used three different doses of Chinese medicinal formulae to treat rats with IgAN. We choosed the best interventional dose of formulae by comparing the differences of expression of renal VEGF and its receptor Flk-1 mRNA and deposition of IgA1 in glomerular mesangial area.3. Forty SD rats were randomly divided into 4 groups: normal control group, model group, valsartan group and the best dose of Chinese medicinal formulae group. After the successful establishment of rat model with IgA nephropathy, each group of rats were administrated with the corresponding medicine respectively for 6 weeks. 24-hour urinary total protein(UTP), serum creatinine(Scr), blood urea nitrogen(BUN) of all rats were detected. Renal pathological changes of rats were observed by electron microscopy and the IgA1 deposition of glomerular mesangial area was detected by immunofluorescence. The mRNA expression of renal VEGF and its receptor Flk-1 were examined by real-time polymerase chain reaction(RT-PCR), and the correlated analysis were performed with biochemical parameters and renal pathological score.Results1. Two modified methods could induce the rat model wih IgAN. But the method of BSA + LPS + CCL4 was better in proteinuria, renal dysfunction, renal pathological changes, and IgA1 deposition of glomerular mesangial area.2. In preliminary experiment, compared with model group, the fluorescence intensity in glomerular mesangial area weakened and the expression of renal VEGF and its receptor Flk-1mRNA decreased in three different dose groups of Chinese medicinal formulae. The effect was best in middle dose group of Chinese medicinal formulae.3. Compared with model group, the level of UTP, Scr and BUN significantly declined, the expression of renal VEGF and its receptor Flk-1mRNA descended, pathological changes weakened and the IgA1 deposition of glomerular mesangial area decreased in treatment groups. The differences were statistically significant(P < 0.01), but these differences were more significant in middle dose group of Chinese medicinal formulae(P < 0.05). The expression of renal VEGF and its receptor Flk-1mRNA showed positive correlation with UTP, Scr, renal vascular lesions, mesangial proliferation, segmental lesions and the infiltration degree of renal interstitial inflammatory cell.Conclusions1. The expression of renal VEGF and its receptor Flk-1mRNA reflected the degree of proteinuria and renal pathological damage in rat with IgAN.2. Qingli Huoxue Yangyin Fang played a interventional role for IgA nephropathy. It may reduce podocyte injury, then decline the expression of renal VEGF and its receptor Flk-1mRNA, deposition of glomerular mesangial abnormal glycosylation IgA1 and pathological changes. It finally reduced the leakage of urinary protein and improved renal function.