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马钱苷对脓毒症大鼠炎症反应及肠道屏障损伤的影响
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王 灿 1, 2* ,李岩涛 ,周 正 ,王璐鹏 ,高媛媛 ,范少希 (1. 河北省中医院重症医学科,石家庄
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050011;2.河北中医药大学临床医学院,石家庄 050011;3.河北省中医院药学部,石家庄 050011;4.河北省中
医院血管外科,石家庄 050011;5.河北省中医院产科,石家庄 050011;6.河北省中医院感染控制科,石家庄
050011)
中图分类号 R965 文献标志码 A 文章编号 1001-0408(2025)05-0574-05
DOI 10.6039/j.issn.1001-0408.2025.05.12
摘 要 目的 探讨马钱苷通过调节Ras同源基因家族成员A(RhoA)/Rho相关卷曲螺旋形成蛋白激酶1(ROCK1)信号通路对脓
毒症大鼠炎症反应及肠道屏障损伤的影响及机制。方法 采用盲肠结扎和穿刺法建立脓毒症大鼠模型,并随机分为脓毒症组、马
钱苷低剂量组(50 mg/kg 马钱苷,灌胃)、马钱苷高剂量组(200 mg/kg 马钱苷,灌胃)、阳性对照组(0.2 mg/kg 阿托伐他汀,腹腔注
射)、马钱苷高剂量+溶血磷脂酸(LPA)组(200 mg/kg马钱苷,灌胃+10 mg/kg RhoA激活剂LPA,腹腔注射),另设假手术组,每组10
只,每6 h给药1次,连续给药4次。末次给药24 h后,检测大鼠血清中炎症因子白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、IL-
1β水平;观察大鼠回肠组织病理学变化并进行Chiu’s肠黏膜损伤评分;检测大鼠回肠组织中D-乳酸、D-氨基酸氧化酶(DAO)、内
毒素水平,闭锁小带蛋白(ZO-1)、闭锁蛋白(Occludin)阳性染色面积百分比以及RhoA、ROCK1的蛋白相对表达水平。结果 与脓
毒症组比较,马钱苷低剂量组、马钱苷高剂量组大鼠的 ZO-1、Occludin 阳性染色面积百分比均显著升高,IL-6、TNF-α、IL-1β、
DAO、D-乳酸、内毒素水平和Chiu’s肠黏膜损伤评分以及RhoA、ROCK1蛋白的相对表达水平均显著降低(P<0.05),大鼠回肠组
织的破坏程度得到缓解,组织水肿及炎性浸润均明显减轻,且马钱苷高剂量组的改善效果均优于马钱苷低剂量组(P<0.05);与马
钱苷高剂量组比较,RhoA激活剂LPA可显著逆转上述指标的变化趋势(P<0.05)。结论 马钱苷能减轻脓毒症大鼠炎症反应及肠
道屏障损伤,其机制与抑制RhoA/ROCK1信号通路有关。
关键词 马钱苷;脓毒症;RhoA/ROCK1信号通路;炎症反应;肠道屏障损伤
Effects of loganin on inflammatory response and intestinal barrier damage in septic rats
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WANG Can ,LI Yantao ,ZHOU Zheng ,WANG Lupeng ,GAO Yuanyuan ,FAN Shaoxi (1. Dept. of
Critical Care Medicine, Hebei Provincial Hospital of Traditional Chinese Medicine, Shijiazhuang 050011,
China;2. Clinical Medical College, Hebei University of Chinese Medicine, Shijiazhuang 050011, China;
3. Dept. of Pharmacy, Hebei Provincial Hospital of Traditional Chinese Medicine, Shijiazhuang 050011, China;
4. Dept. of Vascular Surgery, Hebei Provincial Hospital of Traditional Chinese Medicine, Shijiazhuang 050011,
China;5. Dept. of Obstetrics, Hebei Provincial Hospital of Traditional Chinese Medicine, Shijiazhuang 050011,
China;6. Dept. of Infection Control, Hebei Provincial Hospital of Traditional Chinese Medicine, Shijiazhuang
050011, China)
ABSTRACT OBJECTIVE To investigate the effects of loganin on inflammatory response and intestinal barrier damage in septic
rats by regulating the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil forming protein kinase 1 (ROCK1)
signaling pathway. METHODS A sepsis rat model was established by cecal ligation and puncture, and randomly divided into sepsis
group, loganin low-dose group (50 mg/kg loganin, gavage), loganin high-dose group (200 mg/kg loganin, gavage), positive
control group (0.2 mg/kg atorvastatin, intraperitoneal injection), and loganin high-dose + lysophosphatidic acid (LPA) group (200
mg/kg loganin gavage and intraperitoneal injection of 10 mg/kg RohA activator LPA). An additional sham surgery group was
established. Each group consisted of 10 rats, and medications were administered once every 6 hours for 4 times. After 24 hours of
the last intervention, the levels of serum inflammatory factors interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-1β
were detected. The pathological changes of ileal tissue were observed and Chiu’s intestinal mucosal injury score was also
performed. The levels of intestinal function-lactate
Δ 基金项目 河北省中医药类科研计划课题(No.2022065,No. dehydrogenase (D-lactate), D-amino acid oxidase (DAO) and
2020103) endotoxin, the percentages of zonula occludens-1 protein (ZO-1)
*第一作者 讲师。研究方向:重症医学。E-mail:mga829@163.
and Occludin positive staining area, as well as protein
com
# 通信作者 讲师。研究方向:感染控制。E-mail:lkrc06@163. expressions of RhoA, and ROCK1 were all detected.
com RESULTS Compared with the sepsis group, the percentages
· 574 · China Pharmacy 2025 Vol. 36 No. 5 中国药房 2025年第36卷第5期