Page 98 - 2019年11月第30卷第21期

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 Δ

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喻 振 ，于瑞莲 ，邵佳蔚，杨 哲，王 惠（南京中医药大学药学院，南京 210046）
中图分类号 R932；R965；R285 文献标志码 A 文章编号 1001-0408（2019）21-2973-07
DOI 10.6039/j.issn.1001-0408.2019.21.19

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。
关键词 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
Study on Repair Effect of Artificial Isaria cicadae on Intestinal Mucosal Injury Induced by 5-Fluorouracil
in Rats
YU Zhen，YU Ruilian，SHAO Jiawei，YANG Zhe，WANG Hui（School of Pharmacy，Nanjing University of
TCM，Nanjing 210046，China）

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，
Δ 基金项目：国家自然科学基金资助项目（No.81673918）；江苏省
IFN-γ ，MPO，G-CSF in serum and the level of MDA in
科技厅政策引导类计划（产学研合作）-前瞻性联合研究项目（No.
intestinal were decreased significantly （P＜0.01）. Serum
BY2015008-03）
levels of sIgA and IL-15 in administration groups as well as
＊硕士研究生。研究方向：中药新药开发。E-mail：15651973605
@163.com the expressions of ZO-1 and Claudin-1 in intestinal tissue were
# 通信作者：副教授，硕士生导师，博士。研究方向：中药新药开 increased significantly（P＜0.01）. CONCLUSIONS：Artificial
发。E-mail：yu3ruilian@163.com I. cicadae can repair intestinal mucosal damage caused by

中国药房 2019年第30卷第21期 China Pharmacy 2019 Vol. 30 No. 21 ·2973 ·