Department of Anaesthesiology, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China.
Eur Rev Med Pharmacol Sci. 2021 Feb;25(3):1574-1581. doi: 10.26355/eurrev_202102_24867.
The aim of this study was to investigate the influences of propofol on intestinal ischemia/reperfusion (I/R) injury in rats through the p38 mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) signaling pathway.
The models of intestinal I/R injury were first successfully established. All rats were randomly divided into 4 groups, namely, S group, I/R group, P group and P + S group. Pathological-morphological changes, injury score and wet-to-dry weight ratio of intestinal tissues as well as oxidative stress indexes in each group of rats were detected. Enzyme-linked immunosorbent assay (ELISA) was applied to measure the levels of inflammatory factors such as creatine kinase-MB (CK-MB), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in each group of rats. Furthermore, Western blotting (WB) assay was applied to determine the protein expression levels of p38 MAPK and NF-κB in different groups.
Intestinal tissue injury was the severest in I/R group, with the infiltration of massive inflammatory cells and oozing of blood (Figure 1A, I/R). Compared with those in I/R group, the infiltration of inflammatory cells and damage to intestinal villi were notably relieved in P group and P + S group, revealing that the intestinal mucosal injury was remarkably repaired in P group and P + S group (Figure 1A, P). Moreover, the intestinal tissue injury score was evidently higher in I/R group, P group and P + S group than that in S group (p<0.05). However, it was markedly lower in P group and P + S group than that in I/R group (p<0.05). I/R group, P group and P + S group exhibited significantly increased wet-to-dry weight ratio of intestinal tissues in comparison with S group (p<0.05). However, P group and P + S group exhibited distinctly lower wet-to-dry weight ratio of intestinal tissues than I/R group (p<0.05). The content of malondialdehyde (MDA) was reduced prominently, while that of superoxide dismutase (SOD) was elevated significantly in P group and P + S group in contrast with those in I/R group (p<0.05). On the contrary, P + S group displayed remarkably lower MDA content and higher SOD content than P group (p<0.05). The levels of CK-MB, TNF-α and IL-6 in the blood rose markedly in I/R group compared with those in S group (p<0.05). However, they declined evidently in P group and P + S group in contrast with those in I/R group (p<0.05). Besides, the protein expression level of phosphorylated p38 MAPK was significantly higher in I/R group, P group and P + S group than that in S group (p<0.05). However, no significant difference was observed in the protein expression of total p38 MAPK among the four groups (p>0.05). However, the protein expression level of phosphorylated p38 MAPK was distinctly down-regulated in P group and P + S group in comparison with that in I/R group (p<0.05). Finally, I/R group, P group and P + S group had a prominently higher protein expression level of NF-κB than S group (p<0.05). However, P group and P + S group exerted a significantly lower protein expression level of NF-κB than I/R group (p<0.05).
Propofol decreases the release of inflammatory factors and alleviates intestinal edema by inhibiting the p38 MAPK/NF-κB signaling pathway, thereby mitigating and treating the intestinal I/R injury in rats.
本研究旨在通过丝裂原活化蛋白激酶(MAPK)/核因子-κB(NF-κB)信号通路探讨异丙酚对大鼠肠缺血再灌注(I/R)损伤的影响。
首先成功建立肠 I/R 损伤模型。所有大鼠随机分为 4 组,即 S 组、I/R 组、P 组和 P+S 组。检测各组大鼠肠组织病理形态学变化、损伤评分和湿干重比以及氧化应激指标。采用酶联免疫吸附测定(ELISA)法测定各组大鼠肌酸激酶同工酶-MB(CK-MB)、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)等炎症因子水平。此外,采用 Western blot(WB)法测定各组大鼠 p38 MAPK 和 NF-κB 蛋白表达水平。
I/R 组肠组织损伤最严重,大量炎性细胞浸润,血液渗出(图 1A,I/R)。与 I/R 组相比,P 组和 P+S 组炎性细胞浸润和肠绒毛损伤明显减轻,表明 P 组和 P+S 组肠黏膜损伤明显修复(图 1A,P)。此外,与 S 组相比,I/R 组、P 组和 P+S 组的肠组织损伤评分明显升高(p<0.05)。但与 I/R 组相比,P 组和 P+S 组明显降低(p<0.05)。I/R 组、P 组和 P+S 组肠组织湿干重比明显高于 S 组(p<0.05)。但与 I/R 组相比,P 组和 P+S 组明显降低(p<0.05)。与 I/R 组相比,P 组和 P+S 组丙二醛(MDA)含量明显减少,超氧化物歧化酶(SOD)含量明显升高(p<0.05)。但与 P 组相比,P+S 组 MDA 含量明显降低,SOD 含量明显升高(p<0.05)。与 S 组相比,I/R 组大鼠血 CK-MB、TNF-α和 IL-6 水平明显升高(p<0.05)。但与 I/R 组相比,P 组和 P+S 组明显降低(p<0.05)。此外,与 S 组相比,I/R 组、P 组和 P+S 组磷酸化 p38 MAPK 蛋白表达水平明显升高(p<0.05)。但四组间总 p38 MAPK 蛋白表达无明显差异(p>0.05)。但与 I/R 组相比,P 组和 P+S 组磷酸化 p38 MAPK 蛋白表达水平明显降低(p<0.05)。最后,与 S 组相比,I/R 组、P 组和 P+S 组 NF-κB 蛋白表达水平明显升高(p<0.05)。但与 I/R 组相比,P 组和 P+S 组 NF-κB 蛋白表达水平明显降低(p<0.05)。
异丙酚通过抑制 p38 MAPK/NF-κB 信号通路减少炎症因子的释放,减轻肠水肿,从而减轻和治疗大鼠肠 I/R 损伤。