大承气汤抑制高迁移率族蛋白1-Toll样受体4信号通路减轻炎症反应改善重症胰腺炎大鼠肾损伤

The protective effect of Da-cheng-qi decoction on kidney injury in rats with severe pancreatitis through suppressing HMGB1-TLR-4/NF-κB-mediated inflammatory response

目的研究大承气汤(DCQD)对重症急性胰腺炎(SAP)大鼠肾损伤的作用及机制。方法60只SD大鼠按随机数字表法分为假手术组(Sham)、SAP组,DCQD治疗组和r-HMGB1组各15只。经胰胆管逆行注射牛磺胆酸钠构建大鼠SAP模型。评估各组肾脏病理形态,血清中淀粉酶(AMS)、脂肪酶(LIS)、肌酐(Cr)、尿素氮(BUN)和高迁移率族蛋白1(HMGB1)含量,血清和肾脏白介素-6(IL-6)、单核细胞趋化蛋白-1(MCP-1)和肿瘤坏死因子-α(TNF-α)表达及肾脏HMGB1、乙酰化HMGB1(Acetyl-HMGB1)、Toll样受体4(TLR4)、Myd88、p-p65和p65蛋白表达。结果与Sham组比较,SAP组肾脏病理损伤加重,AMS、LIS、Cr、BUN、HMGB1、IL-6、MCP-1、TNF-α、Acety-HMGB1、TLR4、Myd88和p-p65的表达增高(P<0.05);与SAP组比较,DCQD组肾脏病理损伤减轻,AMS、LIS、Cr、BUN、HMGB1、IL-6、MCP-1、TNF-α、Acety-HMGB1、TLR-4、Myd88和p-p65的表达降低(P<0.05);与DCQD组比较,r-HMGB1组肾脏病理损伤加重,AMS、LIS、Cr、BUN、HMGB1、IL-6、MCP-1、TNF-α、Acety-HMGB1、TLR-4、Myd88和p-p65的表达增高(P<0.05)。四组间p65表达比较,差异无统计学意义(P>0.05)。结论大承气汤对SAP诱发的肾损伤有保护作用,其作用机制与促进HMGB1去乙酰化修饰,继而抑制HMGB1-TLR-4/NF-κB介导的炎症反应相关。

Objective To explore the effect and mechanism of Da-cheng-qi decoction(DCQD)on kidney injury in severe acute pancreatitis(SAP)rats.Methods Sixty SD rats were divided into sham group,SAP group,DCQD group,and high mobility group protein 1(r-HMGB1)group,15 in each group.The SAP model was induced by retrograde injection of sodium taurodeoxycholate through the pancreatic biliary tract.The pathological morphology of kidney,the contents of serum amylase(AMS),lipase(LIS),creatinine(Cr),urea nitrogen(BUN)and HMGB1,the expressions of interleukin 6(IL-6),monocyte chemoattractant protein-1(MCP-1)and tumor necrosis factor-α(TNF-α)in serum and kidney,and the expressions of HMGB1,acetyl-HMGB1,toll-like receptor Body 4(TLR-4),myeloid differentiation factor88(MyD88),p-p65 and p65 in kidney were evaluated.Results Compared with the sham group,the SAP group had more serious pathological damage of kidney and higher expressions of AMS,LIS,Cr,BUN,HMGB1,IL-6,MCP-1,TNF-α,Acety-HMGB1,TLR-4,Myd88 and p-p65(P<0.05).Compared with the SAP group,the DCQD group had lighter pathological damage of kidney and less expression of above indexes(P<0.05).Compared with the DCQD group,the r-HMGB1 group had more serious pathological damageofkidney and higher expression of the above indexes(P<0.05).In addition,there was no difference in p65 expression among the four groups(P>0.05).Conclusion DCQD can attenuate kidney injury induced by SAP.Its mechanism is related to the significant inhibition of HMGB1-TLR-4/NF-κB-mediated inflammatory response in SAP though down-regulating acetylation of HMGB1.