The Study Of Fasudil Hydrochloride Prevented Acute Kidney Injury Rat Caused By Lipopolysaccharide

ObjectiveEstablished acute renal injury model by intraperitoneal injection of lip polysaccharide, and investigated the effects of Fasudil hydrochloride on tumor necrosis factor-alpha,Endothelin-1,Rho kinases-Ⅰand Nuclear Transcription Factor of Kappa B p65 of the acute renal injury renal tubular epithelia cells.MethodsSixty-five male Wister rats were randomly divided into three groups: control group, AKI group and treatment group. The five rats were injected with normal sodium 1 ml via intraperitoneal in control group. The AKI group was randomly divided into six groups (1h,6h,12h,24h,48h,72h), and there were 5 rats in each group. With LPS 6 mg/kg via intraperitoneal to establish AKI model in AKI group. The treatment group was then randomly divided into six groups (1h,6h,12h,24h,48h,72h), and there were 5 rats in each group. With Fasudil 30 mg/kg via intraperitoneal 1 hour before injection with LPS in treatment group, and With Fasudil 30 mg/kg/d via intraperitoneal in 48h group and 72h group. The rats were observed 1h-72h according to different time points and were killed at corresponding time points. The levels of plasma lip polysaccharide, cretonne and serum urea nitrogen were determined, and the contents of tumor necrosis factor-alpha (TNF-α) and Endothelin-1 (ET-1) were determined by Enzyme-linked immunosorbent assay. The expressions of Rho kinases-Ⅰ(ROCK-Ⅰ) and Nuclear Transcription Factor of Kappa B p65 (NF-κB p65) were observed in renal tubular epithelial cells with immunohistochemisal method.Results1 Compared with the results of control group, CRE,BUN significantly increased at 6h (P<0.05), peaked at 24h and significantly decreased at 48h in AKI group. But there was no significant change in treatment group. And compared with that in AKI group, CRE,BUN significantly decreased at 12h and 24h (P<0.01) in treatment group.2 Compared with that the results of in control group, TNF-αsignificantly increased at 1h (P<0.01) and rapidly decreased in AKI group. TNF-αdid not change significantly at each time point in treatment group. Compared with that in AKI group, TNF-αsignificantly decreased at 1 h (P<0.01)in treatment group.3 Compared with that the results of in control group, ET-1 significantly increased at 1h (P<0.01), peaked at 12h and decreased in AKI group.4 The plasma lip polysaccharide level significantly increased at 1h, peaked at 6h and significantly decreased at 12h in AKI group, there was no statistical difference at each time point in AKI group and treatment group.5 The expression of ROCK-Ⅰin the control group showed slightly in renal tubule epithelial cell. Compared with that in control group, ROCK-Ⅰsignific-antly increased at 1h (P<0.05), peaked at 12h and decreased at 24h in AKI group. ROCK-Ⅰin the 6h,12h,24h,48h was significant different compared to the same time points in the treatment group.6 The expression of NF-κB p65 in the control group showed slightly in glomerular and tubular. NF-κB p65 significantly increased at 1h, peaked at 12h and significantly decreased at 24h in AKI group. NF-κB p65 in the 1h,6h,12h, 24h was significant different compared to the same time points in the treatment group.7 The renal tubule epithelium showed large and of the fatty degeneration and vacuolar degeneration in the early in AKI group. There were different levels of renal tubule epithelial cell necrosis, nuclear psychosis, dissolve and disappeared. The necrotic renal tubule epithelial cell shaded into the lumen and formatted fuzzy granular structure. There were congestion, edema and inflammated cell infiltration in the infestation around the renal tubule. The inflammation reaction of kidney in treatment group was lighter than in AKI group.8 Compared with that in control group, tubular necrosis score significantly increased at 1h (P<0.01), peaked at 24h in AKI group. Tubular necrosis score at each time point in AKI group were statistically significant compared with that in control group.ConclusionFasudil may reduce the expression of pro-inflammatory TNF-αand ET-1 by attenuation of Rho/Rho kinase and NF-κB p65 signaling, hence its protect-ion protect against LPS-induced AKI in rats.