The Effect Of Simvastatin On NF-κB And Inflammatory Mediators Expression When The Rats Hyperlipidemia Merger Acute Edematous Pancreatitis

Abstract: Objective: Investigate the expression changes on NF-κB in pancreatic tissue and serum TNF-α,IL-6,when hyperlipidemia merger acute edematous pancreatitis; Study the effect on NF-κB and expression of inflammatory mediators after Simvastatin pretreatment and (or) Octreotide treatment. Methods: 30 healthy adult male SD rats were randomly divided into control group(A group),Positive control group(B group), Simvastatin pretreatment group(C group),Octreotide intervention group(D group) and the combined intervention group(E group),n = 6. High fat diet and high-dose intraperitoneal injection of L-arginine to establish the hyperlipidemia merger acute edematous pancreatitis animal models. After 24 hours,collect the specimens,when all the rats were made to double models. Use automatic biochemical analyzer to detect the serum amylase (AMY),triglyceride(TG) and total cholesterol(TC).HE staining of pancreatic tissue to pathological score under the microscope. Adopt double-antibody sandwich ELISA to detect the serum levels of TNF-αand IL-6. Use immunohistochemical to detect the expression of pancreatic tissues NF-κB/p65. Data adopt mean±standard-deviation(ˉx±s) to show, statistical software was used SPSS17.0; The sample mean compared use the single factor analysis of variance(If there was homogeneity of variance,one-way ANOVA analysis was used, If there was heterogeneity of variance H test was used.). Using linear correlation analysis between the degree of correlation;Inspection standardα=0.05, If P<0.05, difference is considered statistically significant. Result:⑴Blood serum biochemical index:①Serum TG of group A below group B and group D (P<0.01), below group C (P<0.05) and group E (P>0.05); Serum TG of B group higher than C group (P<0.05), D group (P>0.05) and E group (P<0.01); In the three intervention groups, group C and E group in reduce serum TG no statistically significant.②Serum TC of group A below group B and group D (P<0.01), below group C (P<0.05) and E group (P>0.05); Serum TC of B group higher than D group (P>0.05), C group and E group (P<0.01); In the three intervention groups, group C and E group in reduce serum TC no statistically significant.③Serum AMY of group A below B group (P<0.01), below group C and group D (P<0.05) , below group E (P>0.05); Serum AMY of B group higher than C group, D group (P<0.05) and E group (P<0.01); Three intervention groups have no statistically significant ,on reduction of serum AMY.⑵The observation of pathology:①General view: Group A pancreas has not seen the abnormal changes; Group B pancreas hypertrophy, capsule tension and oedema obvious; All treatment groups has reduced the hyperemia and edema of pancreatic tissue.②Under Light microscope: Group A pancreatic tissue structure is clear;Group B pancreatic tissue, main show is edema, lobules gap increases, acinar cells infiltrating swollen, has inflammation and partly visible limitations fat necrosis; The treatment groups in hyperemia edema, acinar swelling etc were significantly better than Positive control group, it did not see the obvious fat necrosis.③The pathological scores of B group, C group, D group and E group were significantly higher than A group (P<0.01). The pathological scores of three intervention groups (C group, D group and E group) were significantly lower than B group (P<0.01), and three intervention groups were not statistically significant (P>0.05).⑶The serum TNF-αand IL-6 levels of B group, C group, D group and E group were significantly higher than A group (P<0.01).The serum TNF-αand IL-6 levels of three intervention groups were significantly lower than B group (P<0.01), and in the three intervention groups, E group compared with group C and D group were significantly different (P<0.01), no significant difference between group C and D group (P>0.05). Serum TNF-α,IL-6 concentration and pancreas pathological scores were positively correlated (r=0.855,r=0.823,P<0.01).⑷The NF-κB/p65 protein of A group is mainly negative expression, Group B with yellow or tan; The treatment group yellow stain nuclei quantity and colouring less than the group B. The IOD values of NF-κB/p65 positive cells of group B, group C, group D and group E were significantly higher than group A (P<0.01).The IOD values of NF-κB/p65 positive cells of three intervention groups were significantly lower than group B (P<0.01), And in the three intervention groups, group E compared with group C and D group were significantly different (P<0.01 and P<0.05), no significant difference between group C and D group (P>0.05). Pancreatic tissue NF-κB/p65 protein expression and the pancreas pathological ratings, TNF-α, IL-6 concentrations were positively correlated (r=0.774,r=0.901,r=0.885,P<0.01). Conclusion:⑴By the method of high fat diet feeding and intraperitoneal injection of large doses of L-arginine, we successfully constructed the rats model of hyperlipidemia merger acute edematous pancreatitis.⑵TNF-α,IL-6 and NF-κB in the process of pathogenesis of the rats hyperlipidemia merger acute edematous pancreatitis plays an important role.⑶Simvastatin can cure the rats hyperlipidemia merger acute edematous pancreatitis,the mechanism may be related to the inhibition of NF-κB and TNF-α,IL-6 expression on.