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程华初,徐琦,杨茜芸,尹抗抗,谭达全.大承气汤对不完全性肠梗阻模型大鼠回盲部组织病理改变的影响及作用机制研究[J].湖南中医药大学学报英文版,2021,41(11):1669-1675.[Click to copy
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| 大承气汤对不完全性肠梗阻模型大鼠回盲部组织病理改变的影响及作用机制研究 |
| 程华初,徐琦,杨茜芸,尹抗抗,谭达全 |
| (湖南中医药大学, 湖南 长沙 410208;湖南省中医药研究院, 湖南 长沙 410006) |
| 摘要: |
| 目的 研究大承气汤对不完全性肠梗阻模型动物回盲部组织病理改变及炎性物质释放的影响，探讨其作用机制。方法 选用健康SD大鼠120只，雌雄各半，随机分为假手术组、空白组、模型组和大承气汤高、中、低剂量组，每组20只。采用丝线结扎法制备不完全性肠梗阻模型，大承气汤高、中、低剂量组分别给予11.6、5.8、2.9 g/（kg·d）剂量大承气汤灌胃给药，给药体积均为10 mL/（kg·d），空白组、假手术组、模型组灌胃相同体积的0.9%氯化钠注射液，均连续灌胃3 d。采用结肠损伤评分评价回盲部黏膜损伤指数；采用HE染色观察回盲部黏膜形态学改变；采用ELISA法检测血清白细胞介素-1α（IL-1α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-18（IL-18）、一氧化氮合成酶（eNOS）水平；采用qPCR法检测回盲部组织中IL-1ra、IL-1β、IL-1R、eNOS、核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）、凋亡相关斑点样蛋白（ASC）、胱冬肽酶-1（Caspase-1） mRNA含量。结果 模型组大鼠肠组织病理呈现黏膜损伤、隐窝破坏、黏膜水肿、间质水肿、炎性细胞浸润等一系列炎性损伤。与空白组和假手术组比较，模型组黏膜损伤指数均增高（P<0.01或P<0.05），表明造模成功；与模型组比较，大承气汤各剂量组黏膜损伤指数降低（P<0.01或P<0.05）。与空白组和假手术组比较，模型组血清IL-1α、IL-1β、IL-6、IL-18、eNOS水平及肠组织中IL-1ra、IL-1β、IL-1R、eNOS、NLRP3、ASC、Caspase-1 mRNA水平明显升高（P<0.05或P<0.01）。与模型组比较，大承气汤各剂量组大鼠血清IL-1α、IL-1β、IL-6、IL-18、eNOS分泌水平均能不同程度下调（P<0.01），大鼠肠组织NLRP3、eNOS、Caspase-1 mRNA表达水平下调（P<0.05或P<0.01）；大承气汤中、高剂量组大鼠肠组织中IL-1rα、IL-1β、IL-1R、ASC、Caspase-1 mRNA表达降低（P<0.05或P<0.01）；大承气汤低剂量组大鼠肠组织中IL-1rα、IL-1R、Caspase-1 mRNA表达降低（P<0.05或P<0.01）。结论 大承气汤可有效改善不完全性肠梗阻模型大鼠肠组织病理损伤，减轻炎症反应，调节NLRP3、ASC、Caspase-1的失衡。 |
| 关键词: 不完全性肠梗阻 大承气汤 回盲部黏膜损伤 炎性因子 |
| DOI：10.3969/j.issn.1674-070X.2021.11.005 |
| Received:August 17, 2021 |
| 基金项目:湖南省科技厅项目（2015JC3078）。 |
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| Effect and Mechanism Research of Ileocecal Histopathological Changes of Incomplete Intestinal Obstruction Model Rats by Dachengqi Decoction |
| CHENG Huachu,XU Qi,YANG Qianyun,YIN Kangkang,TAN Daquan |
| (Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Hunan Academy of Traditional Chinese Medicine, Changsha, Hunan 410006, China) |
| Abstract: |
| Objective To study the effect of Dachengqi Decoction on the ileocecal histopathological changes and the release of inflammatory substances in animal models of incomplete intestinal obstruction, and to explore its mechanism of action. Methods A total of 120 healthy SD rats were selected, half male and half female, and randomly divided into sham operation group, blank group, model group and Dachengqi Decoction high, medium and low dose groups, with 20 rats in each group. The incomplete intestinal obstruction model was prepared by silk ligation, and the high, medium, and low dose of Dachengqi Decoction group were administered by intragastric administration. The doses were 11.6, 5.8, 2.9 g/(kg·d), respectively, the administration volume was 10 mL/(kg·d), the blank group, sham operation group, and model group were given the same volume of 0.9% sodium chloride injection for 3 consecutive days. The ileocecal mucosal injury index was evaluated by the colon injury score, the morphological changes of the ileocecal mucosa were observed by HE staining, and the serum interleukin-1α (IL-1α) and interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-18 (IL-18), nitric oxide synthase (eNOS) levels were detected by ELISA, and qPCR method was used to detect IL-1ra, IL-1β, IL-1R, eNOS, nucleotide binding oligomerization domain like receptor protein 3 (NLRP3), apoptosis-related spot-like protein (ASC), Caspase-1 mRNA content. Results The pathology of the intestinal tissue of rats in the model group showed a series of inflammatory injuries such as mucosal injury, crypt destruction, mucosal edema, interstitial edema, and inflammatory cell infiltration. Compared with the blank group and the sham operation group, the mucosal injury index score of the model group increased (P<0.01 or P<0.05), indicating that the model was successful. Compared with model group, the mucosal injury index score of Dachengqi Decoction groups was decreased (P<0.01 or P<0.05). Compared with the blank group and the sham operation group, the serum levels of IL-1α, IL-1β, IL-6, IL-18, and eNOS in the model group and intestinal tissues IL-1ra, IL-1β, IL-1R, eNOS, NLRP3, ASC and Caspase-1 mRNA were significantly increased (P<0.01 or P<0.05). Compared with model group, serum levels of IL-1α, IL-1β, IL-6, IL-18, and eNOS in Dachengqi Decoction groups were down-regulated to varying degree levels (P<0.01), the mRNA expression levels of NLRP3, eNOS and Caspase-1 in rat intestine were down-regulated (P<0.05 or P<0.01); the mRNA expression levels of IL-1ra, IL-1β, IL-1R, ASC and Caspase-1 were decreased in Dachengqi Decoction medium dose and high dose groups (P<0.05 or P<0.01); the mRNA expression levels of IL-1ra, IL-1R and Caspase-1 in intestinal tissue of rats in Dachengqi Decoction low dose group decreased (P<0.05 or P<0.01). Conclusion Dachengqi Decoction can effectively improve the pathological damage of intestinal tissue in rats with incomplete intestinal obstruction, reduce inflammation, and regulate the imbalance of NLRP3, ASC, and Caspase-1. |
| Key words: incomplete intestinal obstruction Dachengqi Decoction ileocecal mucosal injury inflammatory factors |
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