Effect Of Penehyclidine Hydrochloride On Expression Of HIF-1α In Renal Injury Induced By Lower Limb Ischemia Reperfusion (I/R)

Background Ischemica-Reperfusion Injury(IRI) of limb is a common pathologica process,wthich not only leads to local skeletal muscle injury but also result in systemic complications, hypoxia inducible factor-1α(HIF-1α) is the principal transcription factor involved in the regulation of adaptive responses to Hypoxia. Recent studies have demonstrated that HIF-1αmay participate the Ischemica-Reperfusion Injury by different mechanism. Penehyclidine Hydrochloride injection is a new development anticholinergic agent,which mainly act on M1 and M3 receptor and has no or less action to N1 and N2 receptor, Recent studies have demonstrated that Penehyclidine Hydrochloride extremely important for stabilization of cell membranes and membranes structural stabilization of mitochondria and lysosome,can decrease lysosome release, inhibited the generation of arachidonic acid metabolites and inflammatory factor shock factor and neutrophil aggregation.but the effect on kindy injury and HIF-1αhave seldom been reported.Objective To investigate the effect of penehyclidine hydrochloric postconditioning on kidney injury and expression of HIF-lain rat after kidney injury induced by lower limb ischemia /reperfusion (I/R) by establishing an adult rat modle of kidney injury induced by limb ischemia-reperfusion. investigate the protective effect of Penehyclidine Hydrochloride on kindy injury induced by lower limb ischemia reperfusion (I/R) and its mechanisms.Methods 72 adult male Wistar rats weighing 230-250g were randomly divided into 3 groups:control group (group C), limb ischemia-reperfusion group (group R/I), Penehyclidine hydrochloride postconditioning group (group P). The animals were anesthetized with Inhalating of 2% isoflurane,and blood flow of bilateral lower limbs was blocked with rubber bands for 3h in group P, group R/I. In group P Penehyclidine hydrochloride 0.15mg/kg was injected via caudal vein at 3 min before reperfusion. The animals were sacrificed and the kidney was respectively removed at 3h of ischemia, and 1,3,6 h of reperfusion. The blood urea nitrogen and creatinine were detected by colorimetric method, plasma tumor necrosis factora(TNF-α) was detected by ELISA method, HIF-1αof renal tissue were detected by immunohistochemistry method. Renal pathological changes were observed by light microscope. Results Compared with group C, the lever of serum BUN Cr,TNF-a and IL-10, the level of HIF-la of kidney tissue were significantly increased and the MDA went up and SOD went down significantly,the kidneys of model rat displayed significant pathologic changes in group I/R (P <0.05), Compared with group I/R, serum BUN,Cr and TNF-adecreased and IL-10 increased significantly, the lever of HIF-1αof kidney tissue were significantly decreased,the level of MDA went down and SOD went up significantly,pathologic changes were improved in group P (P<0.05).Conclusion Penehyclidine hydrochloride can attenuate renal injury and also decrease lever of HIF-1αof kidney tissue induced by lower limb I/R Its protective mechanisms may be related to inhibiting inflammatory reaction and oxygen free radicals release and improve the hypoxia and microcirculation.