Expression And Significance Of ATF4、CHOP-related Endoplasm-icreticulum-stress(ERS) In Acute Kindey Injury Following Rhabdomyolysis(RM) In Rats And To Observe The Effects Of Anisodamine

Objective:High strength or special training,especially in the case of heat and humidity of the environment, can easily cause rhabdomyolysis (RM) and leading to acute kidney injury (AKI). It has become a important factor seriously affect our battle effectiveness.At present,because of its pathogenesis is still unclear and no effective treatment,the fatality rate is as high as50percent. Learn the mechanism of AKI and improve the treatment has significance to improve the battle effectiveness and military medicine.Wu Guangli Earlier research showed that the apoptosis of renanl tubule epithelial cells is the important mechanism of acute renal failure (ARF).So in this study,we established the animal model of acute kidney injury induced by rhabdomyolysis though injecting Glycerol saline to the hind leg muscle of rats,then deteced by immunohistochemistry and Western blot to observe the expression changes of ATF4/CHOP and the effect of Anisodamine on above changes.Methods:(1) Select42healthy SD rats, weighing200-220g. The rats were randomly divided into three groups:control group (CN, n=6), acute kidney injury group (AKI, n=18) and Anisodamine group (AD, n=18). AKI group and AD group based on injection time is divided into three subgroups,1h,6h and24h groups of six rats.(2) The animal model of acute kidney injury induced by rhabdomyolysis was developed though inject Glycerol saline.(3) Plasma urea nitrogen(BUN), creatinine(Cr) were evaluated by blood biochemical examination.(4) Plasma Mb was evaluated by ELISA.(5) The renal histopathology change were observed with light microscope in HE staining.(6) The expressions of ATF4/CHOP in renal tissues were examined by immunohistochemistry and analyzed with the pathological image analysis system.(7) The expression of ATF4/CHOP in renal tissues were detected by the plaques.2、This study did not find that Ezetimibe can reduces plaque macrophages in invasion, but not sure it Whether can through other ways to produce anti-inflammatory and stable plaques. Western blotting.(8) Statistical analysis:All statistical analysis of the experimental data were used SPSS13.0statistical software package, the results were expressed as mean±standard deviation (X±s). Differences were compared using single factor analysis of variance (one-way ANOVA), correlation analysis using Pearson correlation test, the P<0.05was considered statistically significance. Results:(1)BUN、Cr、Mb of AKI group were significantly higher than CN group (p<0.05,p<0.01), the levels of Cr,BUN,MB were increased predominantly in AKI24h (p<0.01),and the level of CK were increased predominantly in AKI6h,the levels of Cr、BUN、MB decreased remarkably in Anisodamine group Compared with same period of AKI group(p<0.05,p<0.01);(2) the pathology of renal tissue was no changes in CN group,Renal tissue pathological changes were increased progressively from AKIlh to AKI24h.(3)①The expression of ATF4detected-by immunohisto-chemistry were significantly increased in AKI1h compared with CN(p<0.01),and the protein level in AKI6h group were the highest and although it decreased in AKI24(p<0.01).The expression in AD was significantly lower than the same period of AKI group (p<0.05,p<0.01).②the protein levels of CHOP in AKI6h,24h groups increased progressively except AKI1h and CN group(p>0.05),and they were higher than those in AD groups (p<0.01).(5) The results of Western blot:The level of ATF4and CHOP were gradually increased from AKI1h to AKI24h,and the level of ATF4and CHOP were respectively maximum in AKI6h and AKI24h.The expression of ATF4and CHOP in AD were decreased compared with same period of AKI groups (p<0.05,p<0.01).(6) Correlation analysis indicated a negative correlation between Mb and ATF4protein expression in AKI group (r=-0.882,P<001)and a positivecorrelation between the Mb and CHOP protein expression (r=0.993,P<001).Conclusions:(1) Injecting Glycerol saline-caused rhabdomyolysis may cause acute kidney injury through activating ERS signal pathway by up-regulate CHOP in renal tissue.(2) Injecting Glycerol saline-caused rhabdomyolysis may though up-regulate ATF4at the early stage to protect renal tissue,but as reaction time extension,the expression of ATF4in renal tissue decreased and resulted acute kidney injury.(3) Anisodamine has a protective effect on AKI which may though decreased CHOP expression in renal tissue.This may be one of the protect mechanisms of Anisodamine.