
浏览全部资源
扫码关注微信
山西中医药大学,山西 晋中 030619
樊青,硕士,从事中药毒理学研究,E-mail:925557972@qq.com
关建红,教授,从事中药毒理学研究,Tel:0351-3179735,E-mail:gjh1688@sina.com
收稿日期:2021-01-16,
网络出版日期:2021-03-30,
纸质出版日期:2021-06-05
移动端阅览
樊青,关建红.豨莶草水洗脱部位对人肺纤维细胞的毒性与药效作用[J].中国实验方剂学杂志,2021,27(11):76-82.
FAN Qing,GUAN Jian-hong.Toxicity and Efficacy of Water-eluted Fraction from Siegesbeckiae Herba Against Human Embryonic Lung Fibroblasts[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(11):76-82.
樊青,关建红.豨莶草水洗脱部位对人肺纤维细胞的毒性与药效作用[J].中国实验方剂学杂志,2021,27(11):76-82. DOI: 10.13422/j.cnki.syfjx.20211192.
FAN Qing,GUAN Jian-hong.Toxicity and Efficacy of Water-eluted Fraction from Siegesbeckiae Herba Against Human Embryonic Lung Fibroblasts[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(11):76-82. DOI: 10.13422/j.cnki.syfjx.20211192.
目的
2
检测不同浓度豨莶草水洗脱部位(SWEF)对MRC-5人肺纤维细胞的毒性作用及对MRC-5细胞
α
7烟碱型乙酰胆碱受体(
α
7nAChR)表达与炎症因子的影响,从而发现豨莶草毒效与药效作用物质基础。
方法
2
以MRC-5细胞为研究对象,采用细胞增殖与活性检测(CCK-8)法结合流式细胞术、台盼蓝染色判定SWEF(1,6,10,20,50 g·L
-1
)对MRC-5细胞的毒效作用;通过测定沉默基因前后
α
7nAChR的表达及炎症因子水平的变化探讨SWEF对MRC-5细胞的药效作用。
结果
2
SWEF(≥6 g·L
-1
)显著降低MRC-5细胞的存活率(
P
<
0.01),促进MRC-5细胞凋亡与坏死(
P
<
0.01),其半数抑制浓度(IC
50
)为6.03 g·L
-1
;MRC-5细胞
α
7nAChR表达与炎症因子检测显示SWEF含有
α
7nAChR激动剂样物质,该物质可增高
α
7nAChR基因和蛋白的表达(
P
<
0.05,
P
<
0.01),降低炎症因子水平(
P
<
0.05,
P
<
0.01),SWEF下调炎症因子的作用可能与其上调
α
7nAChR mRNA表达有关,二者呈负相关(
P
<
0.01)。
结论
2
SWEF(≥6 g·L
-1
)对MRC-5细胞具有显著的毒性作用,药效作用研究证实SWEF含有
α
7nAChR激动剂样物质,该物质可增高
α
7nAChR的表达,降低炎症因子水平,推测过量的
α
7nAChR激动剂样物质可能为豨莶草的毒性成分之一。
Objective
2
To detect the toxicity of water-eluted fraction from Siegesbeckiae Herba (SWEF) at different concentrations against MRC-5 human embryonic lung fibroblasts and its impacts on the expression of
α
7 nicotinic acetylcholine receptor (
α
7nAChR) and inflammatory factors, so as to figure out the active components responsible for toxicity and efficacy.
Method
2
The toxicities of SWEF at 1, 6, 10, 20, and 50 g·L
-1
against MRC-5 cells were determined by cell counting kit-8 (CCK-8) assay combined with flow cytometry and Trypan blue staining. The changes in
α
7nAChR expression and inflammatory factor levels before and after
α
7nAChR gene silencing were detected to reveal the pharmacodynamic effect of SWEF on MRC-5 cells.
Result
2
SWEF (≥6 g·L
-1
) obviously inhibited the viability of MRC-5 cells (
P
<
0.01) and promoted their apoptosis and necrosis (
P
<
0.01), with the half-maximal inhibitory concentration (IC
50
) being 6.03 g·L
-1
. The determination of
α
7nAChR expression and inflammatory factor levels in MRC-5 cells showed that SWEF contained
α
7nAChR agonist-like substance, which enhanced
α
7nAChR mRNA and protein expression (
P
<
0.05,
P
<
0.01) and decreased the inflammatory factor levels (
P
<
0.05,
P
<
0.01). SWEF down-regulated the inflammatory factors possibly by re-regulating
α
7nAChR mRNA expression, exhibiting a negative correlation between them (
P
<
0.01).
Conclusion
2
SWEF (≥6 g·L
-1
) is highly toxic to MRC-5 cells. Pharmacodynamic studies have confirmed that
α
7nAChR agonist-like substance contained in SWEF was responsible for the elevated
α
7nAChR expression and reduced inflammatory cytokines. It is inferred that excessive
α
7nAChR agonist-like substance may trigger the toxicity of
Siegesbeckiae Herba.
国家药典委员会 . 中华人民共和国药典:一部 [M]. 北京 : 中国医药科技出版社 , 2015 : 368 .
关建红 , 薛征 , 任晋斌 . 豨莶草水煎醇沉剂口服小鼠急性毒性 [J]. 中国中药杂志 , 2005 , 30 ( 21 ): 72 - 73 .
高南南 , 杨润梅 , 潘瑞乐 , 等 . 不同物种豨莶草急性毒性的比较 [J]. 毒理学杂志 , 2008 , 22 ( 5 ): 405 - 406 .
关建红 , 薛征 , 任晋斌 . 豨莶草水煎剂小鼠急性毒性及亚急性毒性的实验研究 [J]. 中国实验方剂学杂志 , 2007 , 13 ( 11 ): 49 - 51 .
关建红 , 裴香萍 , 刘秉成 . 豨莶草不同提取部位毒性比较研究 [J]. 山西中医学院学报 , 2009 , 10 ( 1 ): 15 - 16 .
关建红 , 刘炳辰 , 裴香萍 , 等 . 豨莶草活性炭洗脱水溶部位的急性毒性研究 [J]. 山西中医学院学报 , 2012 , 13 ( 1 ): 13 - 14 .
关建红 , 薛征 , 刘炳辰 , 等 . 豨莶草水煎粉剂对小鼠肺毒性研究 [J]. 中国中药杂志 , 2008 , 33 ( 23 ): 101 - 103 .
李玉梅 , 卫洪昌 . ALI/ARDS抗炎治疗研究的策略与展望 [J]. 中国病理生理杂志 , 2009 , 25 ( 4 ): 813 - 816,825 .
宁斌元 , 杨霞 . 胆碱能抗炎通路在急性肺损伤中的作用研究进展 [J]. 中国现代医学杂志 , 2020 , 30 ( 7 ): 69 - 71 .
李杰 , 樊青 , 关建红 . 基于 1 H-NMR代谢组学的豨莶草水洗脱部位致大鼠肺损伤作用机制分析 [J]. 中国实验方剂学杂志 , 2020 , 26 ( 19 ): 204 - 209 .
TANESY E M . Henry dale and the discovery of acetylcholine [J]. C R Biol , 2006 , 329 ( 5/6 ): 419 - 425
YOUNG J W , GEYER M A . Evaluating the role of the alpha-7 nicotinic acetylcholine receptor in the pathophysiology and treatment of schizophrenia [J]. Biochem Pharmacol , 2013 , 86 ( 8 ): 1122 - 1132 .
付帅 , 关建红 . 豨莶草与苍耳子毒效实验研究 [J]. 世界中西医结合杂志 , 2015 , 10 ( 4 ): 493 - 495,498 .
韩庆月 , 胡卓莹 , 刘高阳 , 等 . 浅谈犬急性有机磷农药中毒 [J]. 中国工作犬业 , 2018 ( 7 ): 24 - 26 .
尤启东 , 孙铁民 , 郭丽 . 药物化学 [M]. 8版 . 北京 : 人民卫生出版社 , 2017 : 127 - 128 .
XIE B X , ZHANG G S , ZHANG L R . Advances on α7nAChR as targets for drug development [J]. Chin J Med Chm , 2015 , 25 ( 4 ): 313 - 323 .
吴娟 , 金曼 , 黎笔熙 . 胆碱能抗炎通路在炎性疾病中的应用研究进展 [J]. 医学综述 , 2020 , 26 ( 7 ): 1343 - 1348 .
PINHEIRO N M , SANTANA F P R , ALMEIDA R R , et al . Acute lung injury is reduced by the α7nAChR agonist PNU-282987 through changes in the macrophage profile [J] . FASEB J , 2017 , 31 ( 1 ): 320 - 332 .
LI X , XU Y , CHENG Y , et al . Alpha7 nicotinic acetylcholine receptor contributes to the alleviation of lung ischemia reperfusion injury by transient receptor potential vanilloid type 1 stimulation [J]. J Surg Res , 2018 , 230 ( 1 ): 164 - 174 .
WANG J , LI R , PENG Z , et al . GTS-21 Reduces inflammationin acute lung injury by regulating M1 polarization and function of alveolar macrophages [J]. Shock , 2019 , 51 ( 3 ): 389 - 400 .
0
浏览量
17
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621