Toll样受体在大鼠急性胰腺炎发病中的作用研究

The role of Toll-like receptors in the pathogenesis of acute pancreatitis

目的通过检测Toll受体(TLR)在大鼠急性胰腺炎(AP)胰腺中的表达,探讨TLR在AP炎症启动、AP由水肿向坏死转化、急性坏死性胰腺炎(ANP)肠黏膜损伤革兰阴性细菌的入侵机制。方法 Wistar大鼠42只,随机分为正常对照组、急性水肿性胰腺炎(AEP)组、ANP组、TLR4抗体处理组。检测大鼠胰腺组织形态学变化;TLRs的分布表达规律;血清及腹水胰淀粉酶;胰腺组织干湿比称重;胰腺坏死组织肿瘤坏死因子(TNF)-a、白细胞介素(IL)-1β、IL-6水平。结果与ANP组相比,TLR4抗体处理组胰腺组织坏死区域显著增多,炎性程度显著加重;血清淀粉酶、TNF-a、IL-1β、IL-6测得值在正常对照组与AEP组间、AEP组与ANP组间、ANP组与TLR4抗体处理组间的比较均有统计学差异(P<0.05);胰腺组织TLR蛋白信号表达,正常对照组与AEP组间、AEP组与ANP组间、ANP组与TLR4抗体处理组间的比较均有统计学差异(P<0.05)。结论 TLR在正常大鼠胰腺及血管等均有表达,AP时表达上调,TLR作为天然免疫受体在AP早期炎症启动中起到了重要作用,TLR参与了内毒素信号传递,TLR4在ANP发展过程中起重要的促进作用,进一步阻断内毒互信号通路有可能能改善ANP的预后。

Objective To investigate mechanism of effect of toll-like-receptors（TLR） in acute pancreatitis（AP） enabling,transformation from acute edematous pancreatitis（AEP） into acute necrotic pancreatitis（ANP）,and G_bacteria invasion into damaged intestinal mucosa in ANP with detection of expression of TLR in AP of large mice.Methods 42 Wistar mice were randomly divided into normal control group,AEP group,ANP group and TLR4 antibody handling group.Morphological changes in rat pancreatic tissue,TLRs distribution expression rule,pancreatic amylase of serum and ascites,pancreatic tissue wet and dry weighing,the level of TNF-a,IL-1b,IL-6 were measured and analyzed.Results Compared with the ANP group,pancreatic necrosis area of TLR4 antibody handling group significantly increased.The inflammatory extent was significantly aggravating.Difference of the pancreatic amylase level in serum and ascites,TNF-a,IL-1βand IL-6 were statistically significant（P〈0.05） between normal control group and AEP group,between AEP group and ANP group,between ANP group and TLR4 antibody handling group.Difference of expression number of TLR protein signal expression of Wistar mice was statistically significant（P〈0.05） in between normal control group and AEP group,between AEP group and ANP group,between ANP group and TLR4 antibody handling group.Conclusion TLR expressed in pancreas and vessel of normal Wistar mise,upregulation in acute pancreatitis.TLR is a natural immune receptor and plays an important role in enabling of early imflammation of AP.TLRs take a part in signal transfer of endotoxin.TLR4 plays an important promoting role in ANP development.Further blocking of signal transfer of endotoxin possibly improves ANP prognosis.