| 清解扶正颗粒通过调控NLRP3炎症小体介导的细胞焦亡治疗溃疡性结肠炎 |
| Qingjie Fuzheng Granules treat ulcerative colitis by regulating NLRP3 inflammasome-mediated pyroptosis |
| DOI: |
| 中文关键词: 溃疡性结肠炎,清解扶正颗粒,NLRP3炎症小体,细胞焦亡 |
| 英文关键词: ulcerative colitis, Qingjie Fuzheng granules, NLRP3 inflammasome, pyroptosis |
| 基金项目:福建省自然科学基金(2022J01368) |
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| 中文摘要: |
| 摘要 目的 通过动物实验观察清解扶正颗粒(QFG)对葡聚糖硫酸钠(DSS)诱导的小鼠溃疡性结肠炎(UC)的治疗作用,并探究其作用机制。方法 50只雄性BALB/c小鼠随机分为空白组(Control组)10只和造模组40只,Control组饮用正常水,造模组自由饮用3.5%DSS溶液7d后随机分为DSS组、DSS+QFG组、DSS+NLRP3i组、DSS+5-ASA组,分别给予生理盐水、QFG、CY-09、美沙拉嗪溶液灌胃处理,每日1次,连续7d,隔日测量小鼠体重、粪便隐血及腹泻情况,计算疾病活动指数(DAI);干预结束后测量结肠长度、脾重及脾重指数;苏木精-伊红染色(HE)观察结肠组织形态及病理学评分;Bio-Plex检测血清中IL-1β、IL-6、IL-17、TNF-α含量;RT-qPCR检测结肠组织中NLRP3、Caspase-1、IL-1β、IL-17、IL-18、TNF-α的mRNA表达;Western Blot检测结肠组织中Caspase-1、GsderminD蛋白的表达。结果 与Control组比较,DSS组小鼠体重降低、DAI评分升高、结肠缩短、脾重增加、脾重指数升高(P<0.05),粪便隐血评分升高,结肠隐窝结构破坏、炎症浸润,组织病理学评分升高(P<0.05),血清中IL-1β、IL-6、IL-17、TNF-α含量升高(P<0.05),结肠组织中IL-1β、IL-17、IL-18、TNF-α、NLRP3、Caspase-1的mRNA表达升高(P<0.05),结肠组织中Caspase-1、GsderminD表达升高(P<0.05);与DSS组比较,各给药组体重增加、DAI评分降低、结肠变长、脾重降低、脾重指数下降(P<0.05),粪便隐血评分降低,结肠隐窝结构破坏、炎症浸润改善,组织病理学评分降低(P<0.05),血清中IL-1β、IL-6、IL-17、TNF-α含量降低(P<0.05),结肠组织中IL-1β、IL-17、IL-18、TNF-α、NLRP3、Caspase-1的mRNA表达降低(P<0.05),结肠组织中Caspase-1、Gsdermin蛋白表达降低(P<0.05)。结论 QFG通过调控NLRP3炎症小体及介导的细胞焦亡从而减轻DSS诱导的溃疡性结肠炎。 |
| 英文摘要: |
| Abstract Objective To observe the therapeutic effect of Qingjie Fuzheng Granules (QFG) on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) in mice through animal experiments, and to explore its mechanism of action. Methods Fifty male BALB/c mice were randomly divided into a blank group (Control group) of 10 mice and a model group of 40 mice. The Control group drank normal water, and the model group drank 3.5% DSS solution freely for 7 days and then were randomly divided into DSS group and DS group. The S+QFG group, DSS+NLRP3i group, and DSS+5-ASA group were given physiological saline, QFG, CY-09, and mesalazine solution by intragastric administration, once a day for 7 consecutive days. The body weight, fecal occult blood, and abdominal mass of the mice were measured every other day. Diarrhoea, disease activity index (DAI) was calculated; colon length, spleen weight and spleen weight index were measured after the intervention; colon tissue morphology and pathological scores were observed by hematoxylin-eosin staining (HE); IL-1β, I in serum were detected by Bio-Plex L-6, IL-17, and TNF-α contents; RT-qPCR detection of NLRP3, Caspase-1, IL-1β, IL-17, IL-18, and TNF-α mRNA expression in colon tissue; Western Blot detects the expression of Caspase-1 and GsderminD proteins in colon tissue. Results Compared with the Control group, the mice in the DSS group had reduced body weight, increased DAI score, shortened colon, increased spleen weight, increased spleen weight index (P<0.05), increased fecal occult blood score, destroyed colon crypt structure, inflammatory infiltration, increased histopathological score (P<0.05), increased levels of IL-1β, IL-6, IL-17, and TNF-α in serum (P<0.05), and increased levels of IL-1β, IL-6, IL-17, and TNF-α in colon tissue (P<0.05).The mRNA expression of IL-1β, IL-17, IL-18, TNF-α, NLRP3, and Caspase-1 increased (P<0.05), and Caspase-1 and GsderminD in colon tissue The expression increased (P<0.05); compared with the DSS group, each administration group had increased body weight, decreased DAI score, longer colon, decreased spleen weight, decreased spleen weight index (P<0.05), decreased fecal occult blood score, and destroyed the colon crypt structure. Inflammatory infiltration was improved, histopathological scores were reduced (P<0.05), serum levels of IL-1β, IL-6, IL-17, and TNF-α were reduced (P<0.05), and levels of IL-1β, IL-17, and I in colon tissue were reduced (P<0.05). The mRNA expression of L-18, TNF-α, NLRP3, and Caspase-1 decreased (P<0.05), and the protein expression of Caspase-1 and Gsdermin in colon tissue decreased (P<0.05). Conclusion QFG alleviates DSS-induced ulcerative colitis by regulating NLRP3 inflammasome and mediated pyroptosis. |
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