Effect Of Intermedin On Microvascular Injury Of Unilateral Ureteral Obstruction Rats

Objective:To observe the effect of Intermedin on microvascular injury of renal fibrosis in UUO rat model.Methods:(1)72 healthy male Wistar rats, body weight(200±20) g,. Were randomly divided into Sham group(n=24), UUO group(n=24) and IMD group(n=24, under sterile conditions,the rats dorsal skin incise the approximate1 cm long incision, implant pumps that dissolve IMD8-47 with saline and inject it to mini-osmotic pumps under the sterile conditions. The pumps open towards the rat dorsal anterior, continuously subcutaneous administrate by the doses of 100ng/(kg·h). Group UUO, group IMD were performed UUO rat model, group Sham free ureteral ligation.(2)At the7, 14, 21, 28 day after the operation, 6randomly-selected rats form each of the three groups respectively were blooded by abdominal arotic and their obstructive kidneys were taken out.The renal histopathological changes were observed through HE and Masson staining;the contents of BUN, Scr and Cys C of the obstructive kidneys were determinated; the TGF-β1, α-SMA, BMP-7,E-cadherin, TSP-1 and VEGF on the expression of m RNA were detected by RT-PCR and immunohistochemistry was used to detect the expression of the protein.Results:⑴ Kidney pathological changes:Displayed under light microscope, the shamoperation group rats’ glomerular, renal tubular structure was normal; the rats in UUO group were swelling, vacuolar degeneration of renal tubular epithelial cells, renal tubular atrophy,vascular occlusion or expansion, diffuse monocyte, lymphocyte infiltration, interstitial,renal tubular basement membrane thickening, shrinkage increased, fiber cell proliferation,collagen fiber increased, fibrosis, micro vascular lumen, most are compressed,disintegration, or expansion, lumen structure disappeared, replaced by fibrosis products,the degree of fibrosis obviously, tubular basement membrane thickening of diffuse,shrinkage increased tubulointerstitial damage aggravated. Compared with UUO group,renal tubular damage, interstitial fibrosis of the IMD group are lighter.(2)The BUN, Scr and Cys C levels.:Compared with the sham operation group, serum BUN, Scr and Cys C increased in the UUO group at different time points(P<0.05), obstruction reached peak at21 d, then decreased; compared with UUO group, serum BUN, Scr and Cys C of the IMD group were decreased(P<0.05).(3)The expression of TGF- beta 1,alpha-SMA,BMP-7 and E-cadherin:RT-PCR and immunohistochemistry showed that m RNA and protein expression levels of TGF- beta 1 and alpha-SMA increased significantly in UUO group at4 different time points, compared with the sham operation group(P<0.01). While compared with the UUO group, those of the IMD group decreased(P<0.05). BMP-7,E-cadherin of UUO group decreased,compared to the sham group were(P<0.05), while those of IMD group, compared with UUO group increased(P<0.05).(4)The expression of TSP-1 and VEGF:TSP-1 m RNA and protein expression levels of the rats of UUO group at4 different time points increased, compared with those in the sham operation group(P<0.05), compared with the UUO group, those of IMD group decreased(P<0.05).Compared with sham operation group, the expression of VEGF m RNA and protein levels at different time points in UUO group decreased(P< 0.05), compared with and group UUO, m RNA and protein expression level of both on group IMD increased(P<0.05).Conclusions:IMD can ameliorate the renal interstitial fibrosis,and the mechanism may be related to the fact that mediated VEGF can reduce vascular injury.