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[山柰酚对日本血吸虫感染小鼠肝组织TGF-β1/Smads信号通路的影响]

[Influence of kaempferol on TGF-β1/Smads signal path in liver tissue of mice with Schistosoma japonicum infection].

作者信息

Cai Wen, Zhao Lei, Li Hua-rong, Zhang Shu-ling

出版信息

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi. 2014 Aug;26(4):399-404, 419.

Abstract

OBJECTIVE

To investigate the influence of kaempferol on transforming growth factor(TGF-β1/Smads signal tiransduction in liver tissue of mice with schistosomiasis liver fibrosis.

METHODS

Forty BALB/c mice were randomly divided into a normal control group (8 mice), a praziquantel group (8 mice ), and 4 praziquantel + kaempferol groups with different kaempferol dosages (5, 10, 15, 20 mg/kg respectively, 6 mice each group). Besides the normal control group, all the mice in the other 5 groups were infected with Schistosoma japonicum. After the infection for 6 weeks, the praziquantel group and the 4 praziquantel + kaempferol groups were treated with praziquantel 500 mg/(kg.d) for 2 d, then the mice in the praziquantel group were drenched with normal saline for 6 weeks, and those in the 4 praziquantel + kaempferol groups were drenched with kaempferol 5, 10, 15, 20 mg/kg respectively for 6 weeks. After the treatment, all the animals were sacrificed by the cervical dislocation method, and the area of egg granuloma and the degree of fibrosis in the livers of the mice were observed by HE and Masson staining. The expressions of TGF-β1, Smad2/3, Smad7 proteins were measured by the immunohistochemical method, and the mRNA levels of the 3 proteins were detected by RT-PCR.

RESULTS

Compared with the mice in the praziquantel group, the areas of egg granuloma of the liver of the mice in the 4 praziquantel + kaempferol groups were smaller, and the degrees of the hepatic fibrosis of the mice were lesser, and their expressions of Smad2 and Smad3 at protein and their mRNA levels were significantly lower (all P < 0.05), while the expression of Smad7 at protein and its mRNA level were significantly higher (all P < 0.05).

CONCLUSION

By decreasing the expressions of TGF-β1 and Smad2/3, and increasing the expression of Smad7, kaempferol can significantly reduce the degrees of hepatic fibrosis and granuloma caused by schistosome eggs after the praziquantel treatment.

摘要

目的

探讨山奈酚对日本血吸虫病肝纤维化小鼠肝组织中转化生长因子(TGF-β1/Smads)信号转导的影响。

方法

将40只BALB/c小鼠随机分为正常对照组(8只)、吡喹酮组(8只)和4个不同山奈酚剂量的吡喹酮+山奈酚组(分别为5、10、15、20mg/kg,每组6只)。除正常对照组外,其他5组小鼠均感染日本血吸虫。感染6周后,吡喹酮组和4个吡喹酮+山奈酚组用吡喹酮500mg/(kg·d)治疗2天,然后吡喹酮组小鼠用生理盐水灌胃6周,4个吡喹酮+山奈酚组小鼠分别用5、10、15、20mg/kg山奈酚灌胃6周。治疗后,所有动物采用颈椎脱臼法处死,通过HE和Masson染色观察小鼠肝脏虫卵肉芽肿面积和纤维化程度。采用免疫组织化学方法检测TGF-β1、Smad2/3、Smad7蛋白表达,采用RT-PCR检测3种蛋白的mRNA水平。

结果

与吡喹酮组小鼠相比,4个吡喹酮+山奈酚组小鼠肝脏虫卵肉芽肿面积较小,肝纤维化程度较轻,其Smad2和Smad3蛋白表达及mRNA水平显著降低(均P<0.05),而Smad7蛋白表达及mRNA水平显著升高(均P<0.05)。

结论

山奈酚可通过降低TGF-β1和Smad2/3表达,增加Smad7表达,显著减轻吡喹酮治疗后血吸虫卵引起的肝纤维化和肉芽肿程度。

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