Expression And Significance Of Vascular Endothelial Growth Factor And Its Receptor In The Hepatitis B Virus Associated Nephritis

[Objective]:1. To observe the expression of VEGF, Flk-1 and TM in HBV-GN, and explore their roles in the progress of HBV-GN.2. To observe the expression of ICAM-1, VCAM-1 and TM in different clinical and pathology of HBV-GN,and study their effect in the progress of HBV-GN.3. To investigate the effect of HBV-DNA positive serum from patient with HBV which could not damage kidney and HBV-GN on cell Proliferation and the expression of AT1RmRNA /AT2RmRNAof human mesangial cells, and explore their clinical value in HBV-GN.[Methods]:1. The clinical and pathological data of 68 patients was retrospectively analyzed, who were diagnosed as HBV-GN by renal biopsy. The situations of vascular lesion in nephridial tissue of 68 patients with HBV-GN were observed by double blind method. The protein expression of VEGF, Flk-1, ICAM-1, VCAM-1and TM in renal biopsy specimens were determined by immunohistochemistry, tested by semi-quantitative method, analysed their changes and relation with the clinical pathology, vascular lesion.2. The human mesangial cells were cultured in the presence of the serum of healthy person, the HBV-DNA positive serum from patients with HBV which could not damage kidney and HBV-GN. Proliferation measurement of each group was tested by MTT, and mRNA measurement of AT1RmRNA and AT2RmRNA in each group was tested by RT-PCR.[Results]:1. The expression of VEGF and Flk-1 in HBV-GN was significantly higher than normal control group, and significantly different among different pathological types of HBV-GN. The expression of TM in glomerular capillaries of HBV-GN patients (SGN excluded) was not obviously increased as compared to the control group. In comparison with the control group and other pathology, the expression of TM in SGN group was significantly lower. The expression of VEGF and Flk-1 was positively correlated in glomerulus. Their expression intensity was negatively correlated to the lesion degree of glomerulus between the moderate and severe disease group. The expression of TM was negatively correlated to the lesion degree of glomerulus. The expression of VEGF and TM in sclerosis group was evidently decreased. Their expression intensity was positively correlated in sclerosis group, and was no correlation in non sclerosis group. The expression of VEGF and Flk-1 in moderate and severe vascular lesions was significantly higher than those without vascular disease. The expression of VEGF and Flk-1 was positively correlated with the urine protein quantization in 24 hours between the mild and moderate disease group, and was no correlated in severe disease group. The 24h urine protein in the group of VEGF >6 points was significantly higher than VEGF<4 points and 4～6; while increased serum creatinine in the group of VEGF<4 points was obviously higher than 4～6 and >6 points.2. ICAM-l expressed in glomerular and peritubular capillaries of HBV-GN was no significant difference compared with the control group. The expressions of ICAM-l and VCAM-1 in renal tubules were significantly higher than the normal control group, and significantly different among different pathological types of HBV-GN. The expression of TM in peritubular capillaries of HBV-GN patients (SGN excluded) was not obviously increased as compared to the control group. In comparison with the control group and other pathology, the expression of TM in SGN group was significantly lower. The expression of ICAM-1 and VCAM-1 was positively correlated to the lesion degree of renal tubulointerstitium. The expression of TM was negatively correlated to the lesion degree of renal tubulointerstitium. The expression of ICAM-1 and VCAM-1 in severe vascular lesions was significantly higher than those without vascular disease; the expression of TM was adverse to ICAM-1, the least in severe vascular disease. The incidence of hypertension and renal insufficiency in 68 cases of HBV-GN patients with severe vascular disease was higher than those without vascular disease, 24h urinary protein, triglycerides and cholesterol were increased also. The levels of vascular lesions in HBV-GN were significantly different in the distribution of pathological types. The incidence of vascular disease in MN and MCD was lower than MPGN, IgAN, SGN(P<0.01); The incidence of vascular disease in MPGN, IgAN also lower than SGN(P<0.01).3. Normal human serum could stimulate mesangial cells proliferation. There were no differences at all time points. Two HBV-DNA positive serums form the patients carrying HBV without renal damage and HBV-GN patients could significantly stimulate mesangial cells proliferation, which high concentration group in 48h and 72h were significantly different from the normal control group. However, there were no significant difference between two groups induced with two HBV-DNA positive serums from the patients carrying HBV without renal damage and HBV-GN patients. From single indicator, the changes in the expression of AT1RmRNA and AT2RmRNA of mesangial cells induced with two HBV-DNA positive serums form the patients carrying HBV without renal damage and HBV-GN patients were significantly different form the control group. But there were no significant difference between two groups. According to the ratio of AT1RmRNA/AT2RmRNA, the ratio of AT1RmRNA/AT2RmRNA was significantly increased by induced with two HBV-DNA positive serum form the patients carrying HBV without renal damage and HBV-GN patients. The ratio of AT1RmRNA/AT2RmRNA in the high concentration group in 48h and 72h of HBV-GN patients was obviously higher than the patients carrying HBV without renal damage.[Conclusion]:1. VEGF and its receptor play an important role in the pathological progression of HBV-GN. In the early lesions, VEGF and its receptor may be up to promote the formation of proteinuria. In the late lesions VEGF and its receptor were decreased, affecting angiogenesis, regeneration, and increasing synthesis of extracellular matrix.2. The expression of ICAM-1 and VCAM-1 were increased in renal tubular of HBV-GN, inducing infiltration of mononuclear macrophages. ICAM-1 and VCAM-1 may lead to renal tubular immunopathological injury and progression of disease. The expression of TM in renal tissue could not fully reflect the extent of damage of vascular endothelial cells.3. High titers of HBV-DNA positive serum in patients with HBV-GN could lead to the disproportionate expression of mesangial AT1RmRNA/AT2RmRNA, which may be involved in cell proliferation, promotion of glomerular sclerosis,renal interstitial fibrosis.