人工蝉花对5-氟尿嘧啶诱发大鼠肠黏膜损伤的修复作用研究
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篇名: 人工蝉花对5-氟尿嘧啶诱发大鼠肠黏膜损伤的修复作用研究
TITLE:
摘要: 目的:研究人工蝉花对5-氟尿嘧啶(5-FU)诱发大鼠肠黏膜损伤的修复作用。方法:将40只SD大鼠随机分为正常组(生理盐水)、模型组(生理盐水)和人工蝉花高、中、低剂量(3.5、1.75、0.875 g/kg)组,每组8只。除正常组外,其余各组大鼠每日腹腔注射30 mg/kg的5-FU(0.25 g/10 mL)1次,连续5 d;同时,各组大鼠每天灌胃相应药物/生理盐水1次,连续给药8 d。给药结束后,测定各组大鼠体质量变化,苏木精-伊红染色后观察各组大鼠小肠组织病理学变化,并检测各组大鼠生物屏障相关因子[血清中内毒素(ET)、D-乳酸(D-LA)]水平和免疫屏障相关因子[血清中肿瘤坏死因子α(TNF-α)、γ-干扰素(IFN-γ)、分泌性免疫球蛋白(sIgA)、白细胞介素15(IL-15)、集落刺激因子(G-CSF)和小肠组织中髓过氧化物酶(MPO)、丙二醛(MDA)]水平以及机械屏障相关因子(肠表面闭锁小带蛋白ZO-1和紧密连接蛋白Claudin-1)水平。结果:与正常组比较,模型组大鼠体质量显著减少(P<0.01);肠绒毛剥落明显,隐窝结构散乱,大量炎性细胞聚集,肠黏膜损伤严重;血清中D-LA、ET和TNF-α、IFN-γ、MPO、G-CSF水平以及小肠组织中MDA水平均显著升高(P<0.01);血清中sIgA、IL-15水平以及小肠组织中ZO-1、Claudin-1蛋白表达水平显著降低(P<0.05或P<0.01)。与模型组比较,人工蝉花高剂量组大鼠体质量均显著增加(P<0.01);各给药组大鼠小肠的病理变化均得到不同程度改善,其中人工蝉花高、中剂量组小肠形态接近正常组;各给药组大鼠血清中D-LA、ET和TNF-α、IFN-γ、MPO、G-CSF水平以及小肠组织中MDA水平均显著降低(P<0.01);各给药组大鼠血清中sIgA、IL-15水平以及人工蝉花高、中剂量组大鼠小肠组织中Claudin-1、ZO-1蛋白表达水平均显著升高(P<0.01)。结论:人工蝉花可从机械屏障、免疫屏障、生物屏障等多个方面修复5-FU所致大鼠肠黏膜损伤。
ABSTRACT: OBJECTIVE: To study the repair effect of artificial Isaria cicadae on intestinal mucosal injury induced by 5-fluorouracil (5-FU) in rats. METHODS: Forty SD rats were randomly divided into normal group (normal saline), model group (normal saline), artificial I. cicadae high-dose, medium-dose and low-dose groups (3.5, 1.75, 0.875 g/kg), with 8 rats in each group. Except for normal group, other groups were given intraperitoneal injection of 5-FU (0.25 g/10 mL) 30 mg/kg, once a day, for consecutive 5 days. At the same time, each group was given relevant medicine/normal saline intragastrically, once a day, for consecutive 8 d. After medication, body weight of rat was determined in each group. HE staining was used to observe the pathological change of small intestine. The levels of biobarrier-related factor [endotoxin (ET), D-lactic acid (D-LA)], immune barrier related factors (TNF-α, IFN-γ, sIgA, IL-15, G-CSF in serum and MPO, MDA in small intestine) and the levels of mechanical barrier related factors (connexin ZO-1 and Claudin-1) were detected. RESULTS: Compared with normal group, body weight of rats in model group was decreased significantly (P<0.01). Intestinal villus exfoliated obviously, the crypt structure was scattered, a large number of inflammatory cells gathered, and intestinal mucosa was seriously damaged. Serum levels of ET and D-LA, the levels of TNF-a, IFN-γ, MPO and G-CSF in serum, MDA level in small intestine were increased significantly (P<0.01). Serum levels of sIgA and IL-15 as well as the expressions of ZO-1 and Claudin-1 in small intestine were decreased significantly (P<0.05 or P<0.01). Compared with model group, body weight of rats in artificial I. cicadae high-dose group was increased significantly (P<0.01). The pathological changes of the small intestine of rats in each administration group were improved to varying degrees. The intestine morphology of artificial I. cicadae high-dose and medium-dose groups was close to that of the normal group. The levels of and ET, D-LA, TNF-α, IFN-γ, MPO, G-CSF in serum and the level of MDA in intestinal were decreased significantly (P<0.01). Serum levels of   sIgA and IL-15 in administration groups as well as the expressions of ZO-1 and Claudin-1 in intestinal tissue were increased significantly (P<0.01). CONCLUSIONS: Artificial I. cicadae can repair intestinal mucosal damage caused by 5-FU in respects of mechanical barrier, immune barrier, biological barrier.
期刊: 2019年第30卷第21期
作者: 喻振,于瑞莲,邵佳蔚,杨哲,王惠
AUTHORS: YU Zhen,YU Ruilian,SHAO Jiawei,YANG Zhe,WANG Hui
关键字: 人工蝉花;肠黏膜损伤;5-氟尿嘧啶;大鼠;机械屏障;生物屏障;免疫屏障
KEYWORDS: Artificial Isaria cicadae;Intestinal mucosal injury; 5-Fluorouracil; Rat; Mechanical barrier;Biological?barrier; Immune barrier
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