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[摘要]
目的 探究甘草酸对幼鼠实验性结肠炎的治疗作用及其作用机制。方法 将75只SD大鼠幼鼠随机分为对照组、模型组、柳氮磺胺吡啶组(0.5 g/kg)和甘草酸40、160 mg/kg组,每组各15只,制备实验性结肠炎模型的同时分别灌肠给药,连续7 d。观察大鼠一般情况,HE染色法观察大鼠结肠组织病理学变化并进行疾病活动指数(DAI)评分、黏膜损伤指数(CMDI)评定,酶联免疫法测定血清中白介素-4(IL-4)、白介素-17(IL-17)、白介素-1β(IL-1β)水平,逆转录-聚合酶链反应(RT-PCR)、Western blotting法检测大鼠结肠组织中NLRP3、白介素-1β(IL-1β)、凋亡相关斑点样蛋白(ASC)、半胱天冬酶(caspase-1)表达。结果 与模型组比较,甘草酸组幼鼠体质量逐渐增加,症状改善;炎症细胞浸润有所减少,腺体破坏程度降低;DAI评分、CMDI评分均降低,呈剂量相关性(P<0.05);IL-4水平升高,IL-17、IL-1β水平降低,呈剂量相关性(P<0.05);NLRP3、ASC、caspase-1、IL-1β mRNA表达和蛋白表达均降低,呈剂量相关性(P<0.05)。结论 甘草酸能够治疗大鼠实验性结肠炎,可能与抑制NLRP3通路蛋白表达、降低炎症因子水平有关。
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[Abstract]
Objective To explore the therapeutic effect of glycyrrhizin acid on experimental colitis in young rats and explain its mechanism. Methods Seventy-five SD young rats were randomly divided into normal group, model group, sulfasalazine group (0.5 g/kg), and glycyrrhizic acid groups (40 and 160mg/kg), and each group had 15 rats. The experimental colitis models were prepared and rats were enema administered with drugs for 7 d at the same time. The general situations of rats were observed, the pathological changes of colon tissues in rats were observed by HE staining, and the disease activity index (DAI) score and the colon mucosa damage index (CMDI) were evaluated. The levels of interleukin-4 (IL-4), interleukin-17 (IL-17), and interleukin-1β (IL-1β) in serum were measured by ELISA method, reverse transcription polymerase chain reaction (RT-PCR) and Western blotting (WB) method were used to detect the expressions of NLRP3, interleukin-1β (IL-1β), apoptosis-related speckle shc-like protein (ASC), and caspase (caspase-1) in the colon tissues of rats. Results Compared with the model group, body weight gradually increased and symptoms improved in young rats of glycyrrhizic acid groups, and inflammatory cell infiltration and gland destruction were decreased. The DAI scores and the CMDI score in the glycyrrhizic acid groups were decreased, which positively relates to the dosage (P<0.05). Compared with the model group, the levels of IL-4 in the glycyrrhizic acid groups were increased, and the levels of IL-17 and IL-1β were decreased in a dose-dependent manner (P<0.05). Compared with the model group, the expressions of NLRP3, ASC, caspase-1, IL-1β mRNA and their protein expressions in the glycyrrhizin groups were decreased, and it was dose-dependent (P<0.05). Conclusion Glycyrrhizic acid can be used to treat experimental colitis in rats, which may be related to the inhibition of the expression of NLRP3 pathway protein and the levels of inflammatory factors.
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