Objective: To study the protective effects and mechanisms of total saponins of Codonopsis (TSC) on ulcerative colitis in rats. Methods: Fifty male Wistar rats were randomly divided into 5 groups: control group, model group, salazosulfadiazine (SASP) positive control group (0.3 g/kg), TSC high- and low-dose experimental groups(1.2, 0.4 g/kg). UC rat model was established by trinitrobenzene sulfonic acid (TNBS)/ ethanol enema. After administration for 21 days, the rats' symptoms and signs, disease activity index (DAI), colonic mucosal injury index (CMDI) and colonic tissue morphology were observed. The contents of superoxide dismutase (SOD), malondialdehyde (MDA), inflammatory cytokines interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor (TNF-α) in colon tissues were determined. Protein expression of nuclear nuclear transcription factor-κB (NF-κB) in colon tissues was detected. Finally, the effect of TCS therapy was evaluated. Results: Compared with the control group, the DAI and CMDI scores of the rats in the model group were increased significantly, meanwhile the colonic mucosa was seriously damaged, indicating that the model was successful. Compared with the model group, the TSC high and low dose groups could significantly reduce the DAI and CMDI score (P＜0.05) and improve the colonic mucosa form. TSC also could increase the SOD activity and decrease MDA content in colon tissues(P＜0.05), while inhibit the levels of IL-6 and TNF-α mRNA in the colon tissues and promote the expression of IL-10 mRNA (P＜0.01). At the same time, TSC reduced the expressions of NF-κB protein in the colon (P＜0.01). The TSC high-dose group was superior to the low-dose group (P＜0.05). Conclusion: TSC has significant protective effects on ulcerative colonic mucosal damage in UC rats, and there is a dose-dependent relationship; its mechanism may be related to anti-lipid peroxidation and inhibiting the NF-κB signaling pathway to regulate the release of inflammatory factors.
目的: 探讨党参总皂苷(TSC)对大鼠实验性溃疡性结肠炎(UC)的治疗作用及其作用机制。方法: 50只雄性Wistar大鼠随机分为5组:对照组、模型组、柳氮磺胺嘧啶(SASP)阳性对照组(0.3 g/kg)、TSC高剂量组(1.2 g/kg)、TSC低剂量组(0.4 g/kg),用三硝基苯磺酸(TNBS)/乙醇联合灌肠制作大鼠UC模型,给药21 d后,通过观察大鼠症状和体征、疾病活动指数(DAI)、结肠粘膜损伤指数(CMDI)、结肠组织形态;测定结肠组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、炎症因子白介素-6(IL-6)、白介素-10(IL-10)、肿瘤坏死因子α(TNF-α)的含量;检测结肠组织中细胞核内核转录因子-κB(NF-κB)蛋白表达;最终评价TSC的治疗效果。结果: 与对照组比较,模型组大鼠DAI、CMDI评分显著升高,结肠粘膜损伤严重,说明造模成功。与模型组比较,TSC高低剂量组均能显著降低UC大鼠DAI评分、CMDI评分(P＜0.05);改善结肠黏膜形态;升高结肠组织中SOD活力,降低MDA含量(P＜0.05),抑制结肠组织中IL-6、TNF-α mRNA水平,促进IL-10 mRNA表达(P＜0.01);同时降低结肠中NF-κB蛋白表达(P＜ 0.01),且TSC高剂量组优于低剂量组(P＜0.05)。结论: TSC对UC大鼠结肠黏膜损伤具有显著保护作用,以高剂量组为佳;其机制可能与抗脂质过氧化,抑制NF-κB信号通路从而调控炎性因子的释放有关。.
Keywords: NF-κB; cytokine; rat; total saponins of codonopsis; ulcerative colitis.