血必净注射液对SAP大鼠TLR4信号通路介导肠黏膜屏障功能障碍的影响
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摘要
目的探讨血必净注射液对SAP大鼠TLR4信号通路介导肠黏膜屏障功能障碍的影响。方法 24只SD大鼠随机分成空白组(n=8)、对照组(n=8)和治疗组(n=8)。对照组和治疗组用4.5%牛磺胆酸钠溶液胆胰管逆行注射制备SAP模型,空白组采用等量生理盐水逆行注射。治疗组在造模3 h后经鼠尾静脉注射血必净注射液(3 mL/kg)。三组大鼠造模后观察24 h,然后处死取胰腺和小肠组织送病理检查,采用荧光RT-PCR技术检测TLR4和NF-κB表达水平,采用ELSIA法检测血清TNF-α、IL-6、淀粉酶(AMS)及二胺氧化酶(DAO)水平,比较三组大鼠各项指标。结果对照组和治疗组小肠组织TLR4和NF-κB表达以及血清TNF-α、IL-6、AMS及DAO水平均高于空白组(P>0.05),治疗组小肠组织TLR4和NF-κB表达以及血清TNF-α、IL-6、AMS及DAO水平低于对照组(P<0.05)。结论血必净注射液通过干预SAP大鼠TLR4信号通路,降低小肠组织TLR4和NF-κB的表达,减轻小肠组织的炎症反应,对肠黏膜屏障具有一定的保护作用。
Objective To investigate the effect on intestinal mucosal barrier dysfunction(IBF) of Xuebijing injection mediated by Toll-like receptor 4(TLR4) signal pathway in rats of severe acute pancreatitis(SAP). Methods 24 Sprague Dawley(SD) rats were randomly divided into Sham group(n=8), control group(n=8) and treatment group(n=8). The SAP model was established by retrograde injection of 4.5% sodium taurocholate into the biliopancreatic duct in control group and treatment group, while control group was injected with the same amount of saline. In treatment group, Xuebijing injection(3 mL/kg) was injected via tail vein after 3 h of modeling. All rats were monitored and sacrificed after 24 hours of modeling. Samples of pancreas and intestine were collected for pathologic determination. A fluorescent RT-PCR was used to determine the expression of TLR4 and NF-κB of small intestine. The serum levels of TNF-α, IL-6, amylase(AMS) and diamine oxidase(DAO) were measured by using ELISA. All parameters of three groups were compared. Results The expression of TLR4 and NF-κB of small intestine in control group and treatment group were higher than it in control group(P<0.05), as well as the serum levels of TNF-α, IL-6, AMS and DAO(P<0.05). The expression of TLR4 and NF-κB of small intestine in treatment group were lower than it in control group(P<0.05), as well as the serum levels of TNF-α, IL-6, AMS and DAO(P<0.05). Conclusion Xuebijing injection may not only reduce the expression of TLR4 and NF-κB of small intestine, but also alleviate the inflammation reaction of small intestine by interfering with TLR4 signal pathway, which may have a protective effect on intestinal mucosal barrier in SAP rats.
Objective To investigate the effect on intestinal mucosal barrier dysfunction(IBF) of Xuebijing injection mediated by Toll-like receptor 4(TLR4) signal pathway in rats of severe acute pancreatitis(SAP). Methods 24 Sprague Dawley(SD) rats were randomly divided into Sham group(n=8), control group(n=8) and treatment group(n=8). The SAP model was established by retrograde injection of 4.5% sodium taurocholate into the biliopancreatic duct in control group and treatment group, while control group was injected with the same amount of saline. In treatment group, Xuebijing injection(3 mL/kg) was injected via tail vein after 3 h of modeling. All rats were monitored and sacrificed after 24 hours of modeling. Samples of pancreas and intestine were collected for pathologic determination. A fluorescent RT-PCR was used to determine the expression of TLR4 and NF-κB of small intestine. The serum levels of TNF-α, IL-6, amylase(AMS) and diamine oxidase(DAO) were measured by using ELISA. All parameters of three groups were compared. Results The expression of TLR4 and NF-κB of small intestine in control group and treatment group were higher than it in control group(P<0.05), as well as the serum levels of TNF-α, IL-6, AMS and DAO(P<0.05). The expression of TLR4 and NF-κB of small intestine in treatment group were lower than it in control group(P<0.05), as well as the serum levels of TNF-α, IL-6, AMS and DAO(P<0.05). Conclusion Xuebijing injection may not only reduce the expression of TLR4 and NF-κB of small intestine, but also alleviate the inflammation reaction of small intestine by interfering with TLR4 signal pathway, which may have a protective effect on intestinal mucosal barrier in SAP rats.
引文
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[14] 陈凯.重症急性胰腺炎采取血必净注射液联合乌司他丁的疗效和血清炎症因子水平的临床观察 [J].航空航天医学杂志,2018,29(1):70-72.
[15] 郑蕊,张莉,田然,等.血必净注射液治疗重症急性胰腺炎的Meta分析 [J].中华危重病急救医学,2015,27(8):682- 686.
[2] 郭志国,辛毅.急性胰腺炎发病机制研究新观点 [J].中国全科医学,2018,21(20):2400-2403.
[3] 苏伟,欧娅,杨智,等.血必净注射液对重症急性胰腺炎大鼠肠黏膜屏障损伤的实验疗效 [J].广州医学院学报,2012,40(5):1-3.
[4] SCHMIDT J,RATTER D W,LEWANDROWSKI K,et a1.A better model of acute panereatitis for evaluating therapy [J].Ann Surg,1992,215(1):44-56.
[5] KUO C K.Cartilage tissue engineering:its potential and uses [J].Curr Opin Rheumatol,2006,18(1):64-73.
[6] JAKKAMPUDI A,JANGALA R,REDDY R,et al.Acinar injury and early cytokine response in human acute biliary pancreatitis [J].Sci Rep,2017,7(1):15276.
[7] 赵建锋,杜杰,周淼,等.重症急性胰腺炎肠屏障功能损伤机制研究进展 [J].中国现代医药杂志,2016,18(4):91-94.
[8] 龚利平,陈耿臻.Toll样受体4与重症急性胰腺炎研究新进展 [J].汕头大学医学院学报,2010,23(2):122-123,128.
[9] 颜琼,邓明明.核因子-κB在重症急性胰腺炎肝损伤中的作用 [J].广东医学,2014,35(4):614- 616.
[10] NING J W,ZHANG Y,YU M S,et al.Emodin alleviates intestinal mucosal injury in rats with severe acute pancreatitis via the caspase-1 inhibition [J].Hepatobiliary Pancreat Dis Int,2017,16(4):431- 436.
[11] 朱毅东,史和平,吴云龙.清热解毒通里攻下法辅助西医治疗重症急性胰腺炎疗效及对炎性细胞因子、肠道微生态的影响 [J].现代中西医结合杂志,2018,27(28):3098-3101,3105.
[12] 滕勇生,孙发律,张玮,等.血必净注射液治疗急性胰腺炎作用机制的研究进展 [J].中国中西医结合急救杂志,2015,11,22(6):663- 665.
[13] 王秋阳.乌司他丁、参麦联合治疗急性重症胰腺炎疗效观察 [J].航空航天医学杂志,2016,27(2):159-160.
[14] 陈凯.重症急性胰腺炎采取血必净注射液联合乌司他丁的疗效和血清炎症因子水平的临床观察 [J].航空航天医学杂志,2018,29(1):70-72.
[15] 郑蕊,张莉,田然,等.血必净注射液治疗重症急性胰腺炎的Meta分析 [J].中华危重病急救医学,2015,27(8):682- 686.