摘要
目的基于NF-κB/TLR4信号传导通路探讨γ激动剂罗格列酮对重症急性胰腺炎大鼠肝损伤的保护作用。方法 72只SD大鼠随机分为假手术组(SO组)、SAP模型组、罗格列酮处理组(ROSI组),每组24只,各组再随机分为术后6 h、12 h、24 h组,每组8只。SAP模型组采用腹腔注射L-精氨酸法制备,ROSI组在SAP造模后30 min从股静脉注射10%罗格列酮溶液6 mg/kg,SO组仅腹腔注射等体积生理盐水。制模后观察大鼠肝脏组织病理变化,测定肝组织TLR4、NF-κB、Bax、Bcl-2等因子及外周血TNF-α、IL-1β、IL-6、ALT、AST、LDH含量。结果 ROSI组大鼠肝细胞病理损害较SAP组减轻,肝组织NF-κB、TLR4、Bax、Bcl-2、肝细胞凋亡指数与SAP组比较有明显差异(P<0.05),外周血TNF-α、IL-1β、IL-6、ALT、AST、LDH含量与SAP组比较明显下降(P<0.05)。结论 PPAR-γ激动剂可能通过抑制NF-κB/TLR4信号传导通路的活性,下调下游促炎细胞因子水平,从而减轻急性胰腺炎过程中的肝细胞损伤。
Objective To discover the protective effect of PPAR-γ agonists rosiglitazone on injured liver cells in rats correlate with NF-kappa B/TLR4 signal pathway during severe acute pancreatitis. Methods 72 SD rats were randomly divided into sham operation（SO） group（n=24）, SAP model（SAP） group（n=24）, rosiglitazone（ROSI） group（n=24）. Each group was divided into 6 h, 12 h, and 24 h group（n=8） after operation. SAP rats model were did via peritoneal injection of L-arginine. Rats in ROSI group were injected with 6 mg/kg of 10% rosiglitazone via femoral vein 30 min after SAP models were succeed. Sham group was peritoneal injected of same volume NS as SAP group. Pathological changes of liver tissue after operation, TLR4, NF-κB, Bax, Bcl-2 in liver tissue were tested. Serum TNF-α, interieukin-1β, interieukin-6, ALT, AST, LDH were also determined. Results The pathological injuries of liver cell were relieved in ROSI group compared with SAP group. There were significant differences in NF-κB, TLR4, Bax, Bcl-2 and liver cell apoptosis index between ROSI and SAP group（P〈0.05）. TNF-α, IL-1β, IL-6, ALT, AST and LDH were decreased in ROSI group when compared with those in SAP group（P〈0.05）. Conclusion The liver cell injury during SAP may relived by PPAR-γ agonists, the probable reason is that PPAR-γ agonists suppress NF-kappa B/TLR4 signal pathway, and reduce inflammatory cytokines.
出处
《中国现代医生》
2016年第33期30-33,F0003,共5页
China Modern Doctor
基金
浙江省医药卫生科技计划项目(2014KYA172)
