丙泊酚抑制NF-κB p65的磷酸化缓解葡聚糖硫酸钠诱导的结肠炎小鼠病理损伤和免疫反应

Propofol inhibits the phosphorylation of NF-κB p65 and alleviates the pathological damage and immune response in mice with dextran sodium sulfate induced colitis

为探讨丙泊酚对葡聚糖硫酸钠(dextran sodium sulfate, DSS)诱导的结肠炎小鼠病理损伤和免疫反应的影响,构建DSS诱导的结肠炎小鼠模型,将小鼠随机分为5组:对照组、模型组、丙泊酚低剂量组、丙泊酚中剂量组和丙泊酚高剂量组。采用疾病活动指数评分检测小鼠体质量变化和结肠长度,H-E染色检测病理损伤程度并进行组织病理学评分,末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(terminal dexynucleotidyl transferase-mediated dUTP nick-end labeling, TUNEL)染色检测细胞凋亡情况,qRT-PCR检测IL-1β、IL-6、TNF-α、IL-10 mRNA水平,ELISA检测IL-1β、IL-6、TNF-α、IL-10水平,Western blotting检测p65、p-p65蛋白表达。结果显示,与对照组比较,模型组小鼠体质量显著降低(P<0.05),结肠长度显著缩短(P<0.05),病理学评分显著升高(P<0.05),结肠细胞凋亡率显著增加(P<0.05),IL-1β、IL-6、TNF-α mRNA水平显著升高(P<0.05),IL-10 mRNA水平显著降低(P<0.05),IL-1β、IL-6、TNF-α水平显著升高(P<0.05),p-p65/p65比值显著升高(P<0.05);与模型组比较,丙泊酚中、高剂量组小鼠体质量显著升高(P<0.05),结肠长度显著增加(P<0.05),病理学评分显著降低(P<0.05),结肠细胞凋亡率显著降低(P<0.05),IL-1β、IL-6、TNF-α mRNA水平显著降低(P<0.05),IL-10 mRNA水平显著升高(P<0.05),IL-1β、IL-6、TNF-α水平显著降低(P<0.05),IL-10水平显著升高(P<0.05),p-p65/p65比值显著降低(P<0.05)。该研究提示,丙泊酚通过抑制NF-κB p65的磷酸化缓解DSS诱导的结肠炎小鼠病理损伤和免疫反应。

To investigate the effects of propofol on pathological injury and immune response in mice with colitis induced by dextran sodium sulfate(DSS), mice were randomly divided into 5 groups: the control group, the model group, the low-dose propofol group, the medium-dose propofol group and the high-dose propofol group. The changes of body weight and colon length were measured by disease activity index score;the pathological injury degree and histopathological score were detected by H-E staining;apoptosis was detected by treminal dexynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL) staining;the mRNA levels of IL-1β, IL-6, TNF-α and IL-10 were measured by qRT-PCR;the levels of IL-1β, IL-6, TNF-α and IL-10 were measured by ELISA, and the protein expressions of p65 and p-p65 were detected by Western blotting. The results showed that compared with the control group, the body weight of the model group significantly reduced(P<0.05), colon length decreased significantly(P<0.05), pathology score significantly higher(P<0.05), the apoptosis rate increased significantly(P<0.05), IL-1β, IL-6, TNF-α mRNA levels were significantly increased(P<0.05), IL-10 mRNA level was significantly lower(P<0.05), IL-1β, IL-6, TNF-α expressions significantly increased(P<0.05), and the p-p65/p65 ratio increased significantly(P<0.05). Compared with the model group, the body weight of the propofol middle-and high-dose groups significantly increased(P<0.05), as well as the length of the colon(P<0.05), pathology score decreased significantly(P<0.05), the apoptosis rate was significantly lower(P<0.05), IL-1β, IL-6, TNF-α mRNA levels decreased significantly(P<0.05), IL-10 mRNA level increased significantly(P<0.05), IL-1β, IL-6, TNF-α expressions decreased significantly(P<0.05), IL-10 content increased significantly(P<0.05), the p-p65/p65 ratio was significantly reduced(P<0.05).The study suggests that propofol could alleviate the pathological injury and immune response of mice with colitis induced by DSS via inhibiting the phosphorylation of NF-κB p65.