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[日本血吸虫半胱氨酸蛋白酶抑制剂干预治疗小鼠脂多糖诱导的脓毒症]

[Intervention with Schistosoma japonicum cysteine protease inhibitor for treatment of lipopolysaccharide-induced sepsis in mice].

作者信息

Wan Yong-Kun, Li Hui-Hui, Zuo Lin, Wang Xiao-Li, Wang Li-Yuan, He Wen-Xin, Jiang Hui, Wang Shou-Xiang, Sheng Jie, Zhang Min, Qian Hai-Chun, Yang Fang-Fang, Xie Hong, Gao Shi-Fang, Fang Qiang, Yang Xiao-di, Liu Mu-Ling

机构信息

First Affiliated Hospital, Bengbu Medical College, Bengbu 233000, China.E-mail:

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2018 May 20;38(5):625-629. doi: 10.3969/j.issn.1673-4254.2018.05.20.

Abstract

OBJECTIVE

To observe the effect of Schistosoma japonicum cysteine protease inhibitor (rSjCystatin) for treatment of lipopolysaccharide (LPS)-induced sepsis in mice.

METHODS

After a week of adaptive feeding, 54 BALB/c mice were randomly divided into normal control group (group A), sepsis group (group B), and rSjCystatin intervention group (group C). The mice in group A received an intraperitoneal injection of PBS (100 µL), and those in groups B and C were injected with PBS (100 µL) containing LPS (10 mg/kg); the mice in group C were also intraperitoneally injected with 25 µg sjCystatin in 100 µL PBS 30 min after LPS injection. From each group, 10 mice were randomly selected 24 h after PBS or LPS injection for detecting serum levels of TNF-α, IL-6, and IL-10 using ELISA and the levels of ALT, AST, BUN, and Cr using automatic biochemical analyzer; the pathological changes in the liver, lung and kidney were observed with HE staining. The remaining 8 mice in each group were used for observing the changes in the general condition and the 72-h survival.

RESULTS

The 72-h survival rates of the mice was 100% in group A, 0 in group B, and 36% in group C, showing a significant difference among the 3 groups (P<0.05). Compared with those in group A, the mice in group B exhibited obvious liver, lung, and renal pathologies with increased levels of ALT, AST, BUN, Cr, IL-6, and TNF-α (P<0.05). Treatment with sjCystatin significantly lessened LPS-induced organ pathologies, lowered the levels of liver and renal functional indexes and the pro-inflammatory cytokines, and increased the serum level of IL-10 in the mice (P<0.05).

CONCLUSION

SjCystatin can produce a significant therapeutic effect on sepsis induced by LPS in mice.

摘要

目的

观察日本血吸虫半胱氨酸蛋白酶抑制剂(rSjCystatin)对脂多糖(LPS)诱导的小鼠脓毒症的治疗作用。

方法

适应性喂养1周后,将54只BALB/c小鼠随机分为正常对照组(A组)、脓毒症组(B组)和rSjCystatin干预组(C组)。A组小鼠腹腔注射PBS(100 μL),B组和C组小鼠注射含LPS(10 mg/kg)的PBS(100 μL);C组小鼠在注射LPS 30分钟后还腹腔注射100 μL PBS中含有的25 μg sjCystatin。在注射PBS或LPS 24小时后,从每组中随机选取10只小鼠,用ELISA法检测血清TNF-α、IL-6和IL-10水平,用自动生化分析仪检测ALT、AST、BUN和Cr水平;用HE染色观察肝、肺和肾的病理变化。每组其余8只小鼠用于观察一般状况变化和72小时生存率。

结果

A组小鼠72小时生存率为100%,B组为0,C组为36%,三组间差异有统计学意义(P<0.05)。与A组相比,B组小鼠肝、肺和肾出现明显病变,ALT、AST、BUN、Cr、IL-6和TNF-α水平升高(P<0.05)。sjCystatin治疗显著减轻了LPS诱导的器官病变,降低了肝肾功能指标和促炎细胞因子水平,并提高了小鼠血清IL-10水平(P<0.05)。

结论

SjCystatin对LPS诱导的小鼠脓毒症有显著治疗作用。

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本文引用的文献

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[Effect of excretory/secretory protein of adult worm on CLP-induced sepsis in mice].[成虫排泄/分泌蛋白对CLP诱导的小鼠脓毒症的影响]
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Identifying the immunomodulatory components of helminths.鉴定寄生虫的免疫调节成分。
Parasite Immunol. 2015 Jun;37(6):293-303. doi: 10.1111/pim.12192.

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