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[瘦素对矽肺大鼠肺纤维化的影响及瘦素与低氧诱导因子-1α表达的相关性]

[Effect of leptin on lung fibrosis of silicosis rats and the correlation between leptin and HIF-1α expressions].

作者信息

Pei Houshuang, Li Yongbin, Fan Delong, Zhu Shuyang, Zhang Maowei, Li Huiting, Chen Bi, Zhang Miao, Zhou Ruijuan

机构信息

Department of Respiratory Medicine, Central Hospital of Datun Coal Company, Xuzhou 221611, China.

Department of Respiratory Medicine, Affiliated Hospital, Xuzhou Medical College, Xuzhou 221004, China.

出版信息

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2014 Jul;30(7):700-3.

PMID:25001932
Abstract

OBJECTIVE

To observe the expression of leptin (LP) and its influence on pulmonary fibrosis in experimental rats with silicosis and the correlation between the expressions of leptin and HIF-1α.

METHODS

A total of 120 male Sprague-Dawley rats were randomly divided into normal control group, silicosis model group, LP intervention groups (consisting of LP5, LP10 and LP20 groups according to the concentration of LP). The rats in the normal control group were intratracheally administered 1 mL normal sodium, and the ones in the other groups were intratracheally given 1 mL SiO₂(40 mg/mL) suspension. The rats in LP intervention groups were intraperitoneally injected with leptin 5, 10, 20 ng/kg.d respectively from the first day. Six rats in each group were sacrificed on the 7th, 14th, 21th and 28th day. The expression of LP on the 7th, 14th, 21th and 28th day and the hydroxyproline content on the 28th day in rat lung tissues were measured by ELISA, and the expressions of HIF-1α and LP proteins in the lung tissues of the silicosis model group were measured by Western blotting.

RESULTS

There were significant differences in the expression of LP in the lung tissues at each time point (7th, 14th, 21th and 28th day) among the five groups (F=669.18, 948.67, 1 172.00, 521.55, P<0.05). The LP content in the silicosis model group was significantly higher than that in the normal control group (P<0.05) and the expression of LP in the LP intervention groups were significantly elevated at each time point (P<0.05) as compared with the silicosis model group. Hydroxyproline content on 28th day was (0.89 ± 0.16), (3.14 ± 0.40), (3.78 ± 0.27), (4.35 ± 0.13), (4.87 ± 0.16) mg/g in normal control group, silicosis model group, LP5, LP10 and LP20 intervention groups, respectively. Compared with the normal control group, hydroxyproline content in the silicosis model group significantly increased (P<0.05), and compared with the silicosis model group, hydroxyproline content in LP intervention groups were significantly raised (P<0.05). The significant positive correlations were noted between the expressions of HIF-1α and LP (r=0.876, 0.796, 0.859 and 0.854 at each time, P<0.05).

CONCLUSION

The expression of LP goes up significantly in the lung tissues of rats with silicosis. Addition of exogenous leptin can increase the collagen deposition in the lung tissues; meanwhile leptin has a positive correlation with HIF-1α.

摘要

目的

观察瘦素(LP)在矽肺实验大鼠肺组织中的表达及其对肺纤维化的影响,以及瘦素与缺氧诱导因子-1α(HIF-1α)表达的相关性。

方法

将120只雄性Sprague-Dawley大鼠随机分为正常对照组、矽肺模型组、LP干预组(根据LP浓度分为LP5、LP10和LP20组)。正常对照组大鼠气管内注入1 mL生理盐水,其他组大鼠气管内注入1 mL二氧化硅(SiO₂,40 mg/mL)悬液。LP干预组大鼠从第1天起分别腹腔注射瘦素5、10、20 ng/kg·d。每组在第7、14、21和28天处死6只大鼠。采用酶联免疫吸附测定(ELISA)法检测大鼠肺组织在第7、14、21和28天的LP表达及第28天的羟脯氨酸含量,采用蛋白质免疫印迹法检测矽肺模型组肺组织中HIF-1α和LP蛋白的表达。

结果

五组大鼠肺组织在各时间点(第7、14、21和28天)的LP表达差异均有统计学意义(F = 669.18、948.67、1172.00、521.55,P < 0.05)。矽肺模型组LP含量显著高于正常对照组(P < 0.05),LP干预组各时间点LP表达均较矽肺模型组显著升高(P < 0.05)。正常对照组、矽肺模型组、LP5、LP10和LP20干预组第28天的羟脯氨酸含量分别为(0.89±0.16)、(3.14±0.40)、(3.78±0.27)、(4.35±0.13)、(4.87±0.16)mg/g。与正常对照组比较,矽肺模型组羟脯氨酸含量显著增加(P < 0.05);与矽肺模型组比较,LP干预组羟脯氨酸含量显著升高(P < 0.05)。HIF-1α与LP表达呈显著正相关(各时间点r分别为0.876、0.796、0.859和0.854,P < 0.05)。

结论

矽肺大鼠肺组织中LP表达显著升高。外源性添加瘦素可增加肺组织胶原沉积;同时,瘦素与HIF-1α呈正相关。

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