奥曲肽对TGF-β1诱导大鼠气道平滑肌细胞增殖的影响

doi:10.12047/j.cjap.5604.2018.060

中国应用生理学杂志 ›› 2018, Vol. 34 ›› Issue (3): 254-257.doi: 10.12047/j.cjap.5604.2018.060

奥曲肽对TGF-β1诱导大鼠气道平滑肌细胞增殖的影响

赵旭文¹, 刘春涛²

1. 阆中市人民医院呼吸内科, 四川南充 637400;
2. 四川大学华西医院呼吸内科, 成都 610041

收稿日期:2017-05-25 修回日期:2017-11-02 出版日期:2018-05-28 发布日期:2018-09-08
通讯作者: 刘春涛,Tel:028-85422382;E-mail:taosen666@tom.com E-mail:taosen666@tom.com
基金资助:
刘春涛,Tel:028-85422382;E-mail:taosen666@tom.com

Effects of octreotide on rat airway smooth muscle cell prol iferation induced by TGF-β1

ZHAO Xu-wen¹, LIU Chun-tao²

1. Department of Respiratory Medicine, Langzhong People's Hospital, Nanchong 637400;
2. Department of Respiratory Medicine, Huaxi Hospital of Sichuan University, Chengdu 610041, China

Received:2017-05-25 Revised:2017-11-02 Online:2018-05-28 Published:2018-09-08
Contact: 刘春涛,Tel:028-85422382;E-mail:taosen666@tom.com E-mail:taosen666@tom.com
Supported by:
刘春涛,Tel:028-85422382;E-mail:taosen666@tom.com

摘要/Abstract

摘要： 目的：探讨奥曲肽对转化生长因子-β1（TGF-β1）诱导气道平滑肌细胞（ASMCs）增殖及凋亡的作用，并了解上述作用是否通过含有SH2结构域的蛋白质酪氨酸磷酸酶1（SHP-1）介导。方法：体外培养大鼠气道平滑肌细胞（ASMCs），以TGF-β1、奥曲肽、SHP-1抑制剂NSC87877作为工具药。将ASMCs分为对照组、TGF-β1组、TGF-β1+奥曲肽组、TGF-β1+奥曲肽+NSC87877组，四甲基偶氮唑蓝（MTT）比色法测定ASMCs增殖，Western blot检测磷酸化SHP-1的水平。另将ASMCs分为对照组、0.01 nmol/ml奥曲肽组、0.1 nmol/ml奥曲肽组，Annexin V/P I双标记流式细胞仪分析方法检测细胞凋亡。结果：①TGF-β1组ASMCs的增殖反应高于对照组（P<0.01），TGF-β1+奥曲肽组ASMCs增殖反应显著低于TGF-β1组（P<0.05），TGF-β1+奥曲肽+NSC87877组的增殖反应显著低于TGF-β1+奥曲肽组（P<0.01）；②0.01 nmol/ml奥曲肽组凋亡率显著高于对照组（P<0.01），0.1 nmol/ml奥曲肽组与对照组比较凋亡率无显著差异；③TGF-β1组较对照组p-SHP-1水平显著降低（P<0.05），TGF-β1+奥曲肽组较TGF-β1组p-SHP-1水平稍升高，但差异无统计学意义，TGF-β1+奥曲肽+NSC87877组p-SHP-1水平较其余3组显著降低（P<0.01）。结论：奥曲肽可抑制TGF-β1诱导的ASMCs增生；低剂量奥曲肽促进ASMCs凋亡，较高剂量奥曲肽对ASMCs凋亡无明显影响；奥曲肽抑制ASMCs增生与SHP-1激活无关，可能通过介导生长抑素受体2（SSTR2）作用的其他机制或通过其他生长抑素受体（SSTRs）抑制ASMCs生长。

关键词: 奥曲肽, 转化生长因子-β1, SHP-1, 气道平滑肌细胞

Abstract: Objective: To investigate the effect of octreotide on the proliferation and apoptosis of the rat airway smooth muscles (ASMCs) induced by transforming growth factor β1 (TGF-β1), and whether the SHZ domain-containing protein tyrosine phosphatase-1(SHP-1) is involved in the effect mentioned above or not.Methods: ①The cultured ASMCs were divided into the following 4 groups:control group, TGF-β1 group, TGF-β1+octreotide group and TGF-β1+octreotide+NSC87877group. The proliferation of ASMCs was detected by MTT assay. The level of phospho-SHP-1(Tyr536) was examined by Western blot.②The cultured ASMCs were divided into 3 groups:control group, 0.01 nmol/ml octreotide group and 0.1 nmol/ml octreotide group. Apoptosis of ASMCs was detected by Annexin-V FITC/PI double staining.Results: ①The absorbance (A_{490 nm}) value of TGF-β1 group was higher than that of control group (P<0.01).The A_{490 nm} value of TGF-β1+octreotide group was lower than that of TGF-β1 group (P<0.05) but higher than that of TGF-β1+octreotide+NSC87877 group(P<0.01).②The apoptotic rate of ASMCs in 0.01 nmol/ml octreotide treated group was higher than that in control group (P<0.01). There was no significant difference of opoptosis rate between control and 0.1 nmol/ml octreotide treated group.③The level of p-SHP-1 in TGF-β1 group was lower than that in control group(P<0.01). There were no significant differences between TGF-β1 group and TGF-β1+octreotide group.The p-SHP-1 in TGF-β1+octreotide+NSC87877 group was the lowest in all the groups.Conclusion: ①Octreotide can inhibit rat ASMCs proliferation induced by TGF-β1. ②Low dose octreotide induces ASMCs apoptosis, but high dose octreotide has no significant effect on ASMCs apoptosis. ③The growth inhibitory effect of octreotide is independent of SHP-1 signal pathway.

Key words: octreotide, transforming growth factor β1, SHP-1, airway smooth muscle cells

赵旭文, 刘春涛. 奥曲肽对TGF-β1诱导大鼠气道平滑肌细胞增殖的影响[J]. 中国应用生理学杂志, 2018, 34(3): 254-257.

ZHAO Xu-wen, LIU Chun-tao. Effects of octreotide on rat airway smooth muscle cell prol iferation induced by TGF-β1[J]. CJAP, 2018, 34(3): 254-257.

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奥曲肽对TGF-β1诱导大鼠气道平滑肌细胞增殖的影响

Effects of octreotide on rat airway smooth muscle cell prol iferation induced by TGF-β1

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