探讨NF-κB信号通路抑制剂保护脓毒症大鼠肠道物理屏障功能的研究

Explore NF-κB Signal Pathway Inhibitor Protective the Intestinal Physical Barrier Function in Septic Rats

目的探讨NF-κB信号通路抑制剂保护脓毒症大鼠肠道物理屏障功能的研究。方法本研究利用内毒素腹腔注射制作脓毒症大鼠模型进行的研究。30只SD大鼠随机分为3组,每组10只,以腹腔注射方式给药:正常对照组给予10 mL·kg^(-1)生理盐水。LPS模型组给予LPS 6 mg·kg^(-1)。LPS+PDTC干预组,预先给予PDTC 100 mg·kg^(-1),1 h后给予LPS 6 mg·kg^(-1)。3组大鼠均在给药完毕后6 h取血液和观察肠道组织的病理学变化。采用ELISA法检测血清炎症因子TNF-α、IL-1β、IL-10浓度。结果注射LPS 6 h之后,LPS模型组的TNF-α浓度为(85.03±48.85)ng·L^(-1)、IL-1β浓度为(452.01±283.23)ng·L^(-1)、IL-10浓度为(137.27±107.17)ng·L^(-1);LPS+PDCA干预组大鼠血清的TNF-α浓度为(46.59±27.41)ng·L^(-1)、IL-1β浓度为(261.08±110.15)ng·L^(-1)、IL-10浓度为(215.50±110.30)ng·L^(-1)。模型组和干预组的炎症因子浓度均高于正常对照组(P<0.05)。正常对照组未检测出IL-10。LPS+PDCA干预组血清的TNF-α、IL-1β水平明显低于LPS模型组(P<0.05),IL-10水平高于LPS模型组(P>0.05)。肠道病理结果显示:正常对照组大鼠小肠组织结构正常,肠绒毛结构清晰;LPS模型组和LPS+PDTC干预组,大鼠小肠黏膜层均呈现不同程度的病变,黏膜下层、肌层等均无明显病变。相比LPS模型组,LPS+PDTC干预组大鼠的小肠病变,如黏膜充血、水肿、出血等程度较轻。结论NF-κB信号通路参与了脓毒症患者的肠道上皮组织的炎症反应,早期给予外源性PDTC能够改善脓毒症患者的肠道上皮组织的物理屏障功能,但是仍需进一步探讨其对肠道损伤的保护机制。

OBJECTIVE To explore NF-κB signal pathway inhibitor protective effect on the intestinal physical barrier function in septic rats.METHODS The sepsis rat model was established by intraperitoneal injection of endotoxin.30 SD rats were randomly divided into three groups(10 rats in each group)and administered by intraperitoneal injection.The normal control group was given 10 mL·kg^(-1) normal saline.LPS model group was given LPS 6 mg·kg^(-1).The LPS+PDTC intervention group,was given PDTC 100 mg·kg^(-1) in advance,and LPS 6 mg·kg^(-1) 1 hour later.The rats blood and intestinal tissues of the three groups were taken in 6 hours after administration,and the concentrations of serum inflammatory factor TNF-α,IL-1β and IL-10 were detected by ELISA.The pathological changes of intestinal tissue were observed.RESULTS 6 hours after LPS injection,In LPS model group,the concentration of TNF-αwas(85.03±48.85)ng·L^(-1) and IL-1β was(452.01±283.23)ng·L^(-1) and IL-10 was(137.27±107.17)ng·L^(-1).In LPS+PDCA intervention group,the concentration in serum of rats of TNF-αwas(46.59±27.41)ng·L^(-1) and IL-1β was(261.08±110.15)ng·L^(-1) and IL-10 was(215.50±110.30)ng·L^(-1).The concentrations of inflammatory factors in model group and intervention group were significantly higher than those in normal control group(P<0.05).IL-10 was not detected in the normal control group.In the serum of LPS+PDCA intervention group,the level of TNF-α,IL-1β,IL-10 were significantly lower than that in LPS model group(P<0.05),and the level of IL-10 was higher than that in LPS model group(P>0.05).The results of intestinal pathology showed that the tissue structure of small intestine was normal and the structure of intestinal villi was clear in the normal control group.In LPS model group and LPS+PDTC intervention group,small intestinal mucosa showed different degrees of lesions,and there were no obvious lesions in submucosa and muscle layer.Compared with LPS model group,LPS+PDTC intervention group had less small intestinal lesions,such as mucosal congestion,edema and bleeding.CONCLUSION NF-κB signaling pathway involves the intestinal inflammatory response of patients with sepsis,and exogenous NF-κB signaling pathway inhibitor given early can improve the physical barrier function of intestinal epithelial tissue in patients with sepsis,therefore the protective mechanism against intestinal injury needs to be further explored.