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大承气汤对肠源性脓毒症小鼠的保护作用及机制
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| 篇名： | 大承气汤对肠源性脓毒症小鼠的保护作用及机制 |
| TITLE： | Protective effects and mechanism of Dachengqi decoction on intestinal septic mice |
| 摘要： | 目的 研究大承气汤（DCQD）对肠源性脓毒症小鼠的保护作用，并从Toll样受体4/髓分化因子88（TLR4/MyD88）信号通路探讨其可能机制。方法将SPF级雄性C57BL/6J小鼠分为假手术（Sham）组、假手术+大承气汤高剂量（Sham+DCQD-H）组、模型（CLP）组、大承气汤低剂量（DCQD-L）组、大承气汤高剂量（DCQD-H）组、阳性对照（Positive）组。CLP组、DCQD-L组、DCQD-H组和Positive组小鼠均以盲肠结扎穿刺法建立肠源性脓毒症模型；DCQD-L组和DCQD-H组小鼠在术前3d和术后7d每天分别按4、8g/kg（按生药量计）灌胃给予大承气汤；Positive组在术前2h腹腔注射乌司他丁1次，术后7d每天腹腔注射乌司他丁1次，剂量均为50000U/kg。Sham组和Sham+DCQD-H组仅暴露盲肠，不做结扎及穿刺；Sham+DCQD-H组在术前3d和术后7d每天灌胃给予大承气汤（8g/kg，按生药量计）；Sham组和CLP组每天均灌胃和腹腔注射生理盐水各0.2mL，连续10d。术后7d每天评估小鼠脓毒症严重程度，并评估小鼠7d生存率；末次给药1h后，检测小鼠血清和回肠组织中肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）水平；观察小鼠肝、肺、肾、回肠组织的病理学形态变化；检测小鼠回肠组织中TLR4、MyD88mRNA表达水平。结果与CLP组比较，DCQD-L组、DCQD-H组小鼠脓毒症评分，血清和回肠组织中TNF-α、IL-6水平（DCQD-L组回肠组织中IL-6除外），肝、肺、肾、回肠组织损伤评分，回肠组织中TLR4、MyD88mRNA表达水平均显著降低（P＜0.05或P＜0.01）；7d生存率（DCQD-L组除外）显著升高（P＜0.05）；小鼠肝细胞组织损伤明显改善，炎症浸润和凋亡减少；肺组织损伤有所缓解，肺泡萎缩、出血、水肿均有不同程度的改善；肾组织损伤改善，肾小管管腔扩张减弱；回肠组织损伤及水肿均有明显改善。结论大承气汤对肠源性脓毒症模型小鼠具有保护作用，其作用机制可能与抑制全身炎症、减轻多器官损伤以及下调TLR4/MyD88信号通路有关。 |
| ABSTRACT： | OBJECTIVE To study the protective effects of Dachengqi decoction （DCQD） on intestinal septic mice， and to explore the possible mechanisms from the Toll-like receptor 4（TLR4）/myeloid differentiation factor 88（MyD88） signaling pathway. METHODS The SPF male C57BL/6J mice were randomly divided into Sham group， Sham+DCQD-H group， model （CLP） group， DCQD-L group， DCQD-H group and Positive group. The model of intestinal sepsis was established by cecal ligation and puncture in CLP group， DCQD-L group， DCQD-H group and Positive group. Three days before the operation and seven days after the operation， DCQD-L group and DCQD-H group were given DCQD intragastrically at 4， 8 g/kg （calculated by crude drug）， respectively. Positive group was given ulinastatin intraperitoneally 2 h before operation and 7 d after the operation （at 50 000 U/kg）. In Sham group and Sham+DCQD-H group， only cecum of mice was exposed without ligation and puncture. Sham+DCQD- H group was given DCQD intragastrically （8 g/kg，calculated by crude drug） 3 days before the operation and 7 days after the operation. Both the Sham group and CLP group were given normal saline 0.2 mL intragstrically and intraperitoneally each day， for 10 consecutive days. After the operation， the severity of sepsis was assessed， and the 7 d survival rate of mice was assessed. One hour after the last medication， the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in serum and ileum of mice were determined； the pathological and morphological changes of mice’s liver， lung， kidney and ileum were observed； mRNA expressions of the TLR4 and MyD88 in ileum were tested. RESULTS Compared with CLP group， sepsis score， the levels of TNF-α and IL-6 in serum and ileum （except for IL-6 in ileum of DCQD-L group）， damage score of the liver， lung， kidney and ileum， mRNA expressions of TLR4 and MyD88 in ileum were all decreased significantly in DCQD-L group and DCQD-H group （P＜0.05 or P＜0.01）， while 7 d survival rate （except for DCQD-L group） was increased significantly （P＜0.05）. The damage to liver tissue in mice was significantly improved， and inflammation infiltration and apoptosis were reduced； lung tissue damage had been alleviated， with varying degrees of improvement in alveolar atrophy， bleeding and edema； the renal tissue damage was improved and weakened dilation of renal tubular lumen was weakened； the damage and edema of ileal tissue were significantly improved. CONCLUSIONS DCQD may exert a protective role on intestinal septic model mice. The mechanism may be related to the inhibition of systemic inflammation， the reduction of multiple organ damage， and down-regulation of TLR4/MyD88 signaling pathway. |
| 期刊： | 2023年第34卷第17期 |
| 作者： | 钟旋；李袁袁；林荣锋；姚韵婕；刘伟琼；罗毅平；凌家俊 |
| AUTHORS： | ZHONG Xuan，LI Yuanyuan，LIN Rongfeng，YAO Yunjie，LIU Weiqiong，LUO Yiping，LING Jiajun |
| 关键字： | 大承气汤；脓毒症；炎症因子；器官损伤；Toll样受体4/髓分化因子88信号通路 |
| KEYWORDS： | Dachengqi decoction； sepsis； inflammatory factor； organ damage； TLR4/MyD88 signaling pathway |
| 阅读数： | 56 次 |
| 本月下载数： | 4 次 |
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