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目的探讨牛磺酸对重症急性胰腺炎(severe acute pancreatitis,SAP)大鼠枯否细胞(KCs)P38MAPK的影响以及对分泌促炎细胞因子TNF-α和IL-1β的作用。方法48只SD大鼠采用完全随机法分为假手术对照(SO)组、SAP组、SAP+Taur(牛磺酸)组。SAP模型通过胰胆管逆行注射5%牛磺胆酸钠诱导,造模前SAP+Taur组分别于24、12h从尾静脉内注入牛磺酸(3mmol/L,0.1ml/100g)。假手术或造模后分别于12、24h处死动物,检测其血清中AST、ALT、AMS含量;分离KCs,采用Western blot法检测P38MAPK活化情况,凝胶电泳迁移率法(EMSA)检测KCs中NF-κB DNA的表达,并用ELISA法检测KCs培养上清液中TNF-α和IL-1β蛋白含量。结果SAP组大鼠血清中AST、ALT、AMS含量均较SO组明显升高(P<0.01);而SAP+Taur组血清中AST、ALT、AMS含量与SAP组比较,明显降低(P<0.05)。SAP组各时间点大鼠KCs中p38MAPK活性显著高于SO组(P<0.01),而且NF-κB的表达也明显高于SO组(P<0.01),KCs培养上清液中TNF-α和IL-1β蛋白含量明显高于SO组(P<0.01),但SAP+Taur组大鼠KCs上述指标均显著低于SAP组。结论牛磺酸可以抑制急性胰腺炎时KCs中p38MAPK的活化,减少NF-κB的表达,从而对促炎细胞因子TNF-α和IL-1β的分泌起抑制作用,可能具有临床应用前景。
Objective To investigate the effect of taurine on P38MAPK and the secretion of proinflammatory cytokines TNF-α and IL-1β in Kupffer cell (KCs) in rats with severe acute pancreatitis (SAP). Methods 48 SD rats were randomly divided into sham-operated control (SO) group, SAP group and SAP + Taur (taurine) group. The SAP model was induced by retrograde injection of pancreaticobiliary duct with 5% sodium taurocholate, and taurine (3mmol / L, 0.1ml / 100g) was injected into tail vein from SAP + Taur group at 24 h and 12 h respectively. Animals were sacrificed at 12 and 24 hours after sham operation or model establishment, respectively. The contents of AST, ALT and AMS in serum were detected. KCs were isolated and the activation of P38MAPK was detected by Western blot. EMSA was used to detect NF -κB DNA, and the contents of TNF-α and IL-1β in KCs culture supernatant were detected by ELISA. Results Serum levels of AST, ALT and AMS in SAP group were significantly higher than those in SO group (P <0.01), while the levels of AST, ALT and AMS in SAP + Taur group were significantly lower than those in SAP group ). The p38MAPK activity of KCs in SAP group was significantly higher than that in SO group at each time point (P <0.01), and the expression of NF-κB was also significantly higher than that in SO group (P <0.01) IL-1βprotein content was significantly higher than the SO group (P <0.01), but the indicators of KCs in SAP + Taur group were significantly lower than the SAP group. Conclusion Taurine can inhibit the activation of p38 MAPK in KCs and decrease the expression of NF-κB in acute pancreatitis, which may inhibit the secretion of pro-inflammatory cytokines TNF-α and IL-1β and may have clinical application prospects.