The effects of tanshinone IIA on hypoxia/reoxygenation-induced myocardial microvascular endothelial cell apoptosis in rats via the JAK2/STAT3 signaling pathway

Abstract Objective This study aims to investigate the effects of tanshinone IIA on hypoxia/reoxygenation (H/R)-induced myocardial microvascular endothelial cell (MMEC) apoptosis in rats. Methods MMECs from 10-days aged rats were isolated, cultured and identified, which were then divided into followi...

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Veröffentlicht in:Biomedicine & pharmacotherapy 2016-10, Vol.83, p.1116-1126
Hauptverfasser: Cui, Zhen-Tian, Liu, Jian-Ping, Wei, Wan-Lin
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Wei, Wan-Lin
description Abstract Objective This study aims to investigate the effects of tanshinone IIA on hypoxia/reoxygenation (H/R)-induced myocardial microvascular endothelial cell (MMEC) apoptosis in rats. Methods MMECs from 10-days aged rats were isolated, cultured and identified, which were then divided into following groups: control group, control + tanshinone IIA (50 μM) group, H/R model group, H/R + tanshinone IIA (5 μM) group, H/R + tanshinone IIA (50 μM) pre-treatment group, H/R + AG490 (50 μM) pre-treatment group and H/R + AG490 (50 μM) + tanshinone IIA (50 μM) pre-treatment group. MTT assay, TUNEL staining and flow cytometry were used to measure the cellular viability and apoptosis. Western-blot were performed to detect protein expressions in JAK2/STAT3 signaling pathway. Results Compared with control group, H/R group showed decreased cell viability, increased apoptosis rate, increased proportions of cells into G0/G1 phase, decreased proportions of cells in S phase and G2/M phase, as well as up-regulated expressions of JAK2, STAT3, p53, Bax, Caspase-3, pJAK2 and pSTAT3, and down-regulated Bcl-2 expression (all P < 0.05). Compared with H/R group, H/R + tanshinone IIA (5 μM) group, H/R + tanshinone IIA (50 μM) group H/R + AG490 (50 μM) group and H/R + AG490 (50 μM) + tanshinone IIA (50 μM) group had increased cell viability, decreased apoptosis rate, reduced proportions of cells into G0/G1 phase, elevated proportions of cells in S phase and G2/M phase, as well as down-regulated expressions of JAK2, STAT3, p53, Bax, Caspase-3, pJAK2 and pSTAT3, elevated expression of Bcl-2 (all P < 0.05). The most remarkable changes were observed in H/R + AG490 (50 μM) + tanshinone IIA (50 μM) group. Conclusion Tanshinone IIA may attenuate H/R-induced MMEC apoptosis in rats by inhibiting the JAK2/STAT3 signaling pathway and regulating the expressions of p53, Bax, Caspase-3 and Bcl-2, which may provide a protective effect of tanshinone IIA for MMECs.
doi_str_mv 10.1016/j.biopha.2016.07.054
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fullrecord <record><control><sourceid>elsevier</sourceid><recordid>TN_cdi_elsevier_clinicalkeyesjournals_1_s2_0_S0753332216305777</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S0753332216305777</els_id><sourcerecordid>1_s2_0_S0753332216305777</sourcerecordid><originalsourceid>FETCH-LOGICAL-e210t-8e1bc07b547efe92c317d337b0221db45df6af797c39372c7d9f10ed5ed709ce3</originalsourceid><addsrcrecordid>eNotUEtOwzAUzAIkSuEGLHyBpP40cbNBqio-hUosGtbRi_3SuLh2FKelOQ1XJRWsRqMZzYwmih4YTRhl2WyfVMa3DSR8ZAmVCU3nV9GEylTEQnB-E92GsKeUpplYTKKfokGCdY2qD8TXpAcXGuO8Q7JeL4l3pBlafzYw69Cfhx066I13sXH6qFCTw-AVdNqAJQejOn-CoI4WOoJO-75Be1EUWkug9W3vgwnEONLBWHcyQEYLeVu-89m2WBaCBLNzYI3bkRb65huGu-i6Bhvw_h-n0efzU7F6jTcfL-vVchMjZ7SPF8gqRWWVziXWmHMlmNRCyIpyznQ1T3WdQS1zqUQuJFdS5zWjqFPUkuYKxTR6_MvFseRksCvVOMMosF84YNj7YzcOCyUrAy9pub38ebmTZYKmUkrxCyozd-s</addsrcrecordid><sourcetype>Publisher</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>The effects of tanshinone IIA on hypoxia/reoxygenation-induced myocardial microvascular endothelial cell apoptosis in rats via the JAK2/STAT3 signaling pathway</title><source>Elsevier ScienceDirect Journals</source><creator>Cui, Zhen-Tian ; Liu, Jian-Ping ; Wei, Wan-Lin</creator><creatorcontrib>Cui, Zhen-Tian ; Liu, Jian-Ping ; Wei, Wan-Lin</creatorcontrib><description>Abstract Objective This study aims to investigate the effects of tanshinone IIA on hypoxia/reoxygenation (H/R)-induced myocardial microvascular endothelial cell (MMEC) apoptosis in rats. Methods MMECs from 10-days aged rats were isolated, cultured and identified, which were then divided into following groups: control group, control + tanshinone IIA (50 μM) group, H/R model group, H/R + tanshinone IIA (5 μM) group, H/R + tanshinone IIA (50 μM) pre-treatment group, H/R + AG490 (50 μM) pre-treatment group and H/R + AG490 (50 μM) + tanshinone IIA (50 μM) pre-treatment group. MTT assay, TUNEL staining and flow cytometry were used to measure the cellular viability and apoptosis. Western-blot were performed to detect protein expressions in JAK2/STAT3 signaling pathway. Results Compared with control group, H/R group showed decreased cell viability, increased apoptosis rate, increased proportions of cells into G0/G1 phase, decreased proportions of cells in S phase and G2/M phase, as well as up-regulated expressions of JAK2, STAT3, p53, Bax, Caspase-3, pJAK2 and pSTAT3, and down-regulated Bcl-2 expression (all P &lt; 0.05). Compared with H/R group, H/R + tanshinone IIA (5 μM) group, H/R + tanshinone IIA (50 μM) group H/R + AG490 (50 μM) group and H/R + AG490 (50 μM) + tanshinone IIA (50 μM) group had increased cell viability, decreased apoptosis rate, reduced proportions of cells into G0/G1 phase, elevated proportions of cells in S phase and G2/M phase, as well as down-regulated expressions of JAK2, STAT3, p53, Bax, Caspase-3, pJAK2 and pSTAT3, elevated expression of Bcl-2 (all P &lt; 0.05). The most remarkable changes were observed in H/R + AG490 (50 μM) + tanshinone IIA (50 μM) group. Conclusion Tanshinone IIA may attenuate H/R-induced MMEC apoptosis in rats by inhibiting the JAK2/STAT3 signaling pathway and regulating the expressions of p53, Bax, Caspase-3 and Bcl-2, which may provide a protective effect of tanshinone IIA for MMECs.</description><identifier>ISSN: 0753-3322</identifier><identifier>DOI: 10.1016/j.biopha.2016.07.054</identifier><language>eng</language><subject>Internal Medicine ; Medical Education</subject><ispartof>Biomedicine &amp; pharmacotherapy, 2016-10, Vol.83, p.1116-1126</ispartof><rights>Elsevier Masson SAS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids></links><search><creatorcontrib>Cui, Zhen-Tian</creatorcontrib><creatorcontrib>Liu, Jian-Ping</creatorcontrib><creatorcontrib>Wei, Wan-Lin</creatorcontrib><title>The effects of tanshinone IIA on hypoxia/reoxygenation-induced myocardial microvascular endothelial cell apoptosis in rats via the JAK2/STAT3 signaling pathway</title><title>Biomedicine &amp; pharmacotherapy</title><description>Abstract Objective This study aims to investigate the effects of tanshinone IIA on hypoxia/reoxygenation (H/R)-induced myocardial microvascular endothelial cell (MMEC) apoptosis in rats. Methods MMECs from 10-days aged rats were isolated, cultured and identified, which were then divided into following groups: control group, control + tanshinone IIA (50 μM) group, H/R model group, H/R + tanshinone IIA (5 μM) group, H/R + tanshinone IIA (50 μM) pre-treatment group, H/R + AG490 (50 μM) pre-treatment group and H/R + AG490 (50 μM) + tanshinone IIA (50 μM) pre-treatment group. MTT assay, TUNEL staining and flow cytometry were used to measure the cellular viability and apoptosis. Western-blot were performed to detect protein expressions in JAK2/STAT3 signaling pathway. Results Compared with control group, H/R group showed decreased cell viability, increased apoptosis rate, increased proportions of cells into G0/G1 phase, decreased proportions of cells in S phase and G2/M phase, as well as up-regulated expressions of JAK2, STAT3, p53, Bax, Caspase-3, pJAK2 and pSTAT3, and down-regulated Bcl-2 expression (all P &lt; 0.05). Compared with H/R group, H/R + tanshinone IIA (5 μM) group, H/R + tanshinone IIA (50 μM) group H/R + AG490 (50 μM) group and H/R + AG490 (50 μM) + tanshinone IIA (50 μM) group had increased cell viability, decreased apoptosis rate, reduced proportions of cells into G0/G1 phase, elevated proportions of cells in S phase and G2/M phase, as well as down-regulated expressions of JAK2, STAT3, p53, Bax, Caspase-3, pJAK2 and pSTAT3, elevated expression of Bcl-2 (all P &lt; 0.05). The most remarkable changes were observed in H/R + AG490 (50 μM) + tanshinone IIA (50 μM) group. Conclusion Tanshinone IIA may attenuate H/R-induced MMEC apoptosis in rats by inhibiting the JAK2/STAT3 signaling pathway and regulating the expressions of p53, Bax, Caspase-3 and Bcl-2, which may provide a protective effect of tanshinone IIA for MMECs.</description><subject>Internal Medicine</subject><subject>Medical Education</subject><issn>0753-3322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid/><recordid>eNotUEtOwzAUzAIkSuEGLHyBpP40cbNBqio-hUosGtbRi_3SuLh2FKelOQ1XJRWsRqMZzYwmih4YTRhl2WyfVMa3DSR8ZAmVCU3nV9GEylTEQnB-E92GsKeUpplYTKKfokGCdY2qD8TXpAcXGuO8Q7JeL4l3pBlafzYw69Cfhx066I13sXH6qFCTw-AVdNqAJQejOn-CoI4WOoJO-75Be1EUWkug9W3vgwnEONLBWHcyQEYLeVu-89m2WBaCBLNzYI3bkRb65huGu-i6Bhvw_h-n0efzU7F6jTcfL-vVchMjZ7SPF8gqRWWVziXWmHMlmNRCyIpyznQ1T3WdQS1zqUQuJFdS5zWjqFPUkuYKxTR6_MvFseRksCvVOMMosF84YNj7YzcOCyUrAy9pub38ebmTZYKmUkrxCyozd-s</recordid><startdate>20161001</startdate><enddate>20161001</enddate><creator>Cui, Zhen-Tian</creator><creator>Liu, Jian-Ping</creator><creator>Wei, Wan-Lin</creator><scope/></search><sort><creationdate>20161001</creationdate><title>The effects of tanshinone IIA on hypoxia/reoxygenation-induced myocardial microvascular endothelial cell apoptosis in rats via the JAK2/STAT3 signaling pathway</title><author>Cui, Zhen-Tian ; Liu, Jian-Ping ; Wei, Wan-Lin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-e210t-8e1bc07b547efe92c317d337b0221db45df6af797c39372c7d9f10ed5ed709ce3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Internal Medicine</topic><topic>Medical Education</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cui, Zhen-Tian</creatorcontrib><creatorcontrib>Liu, Jian-Ping</creatorcontrib><creatorcontrib>Wei, Wan-Lin</creatorcontrib><jtitle>Biomedicine &amp; pharmacotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cui, Zhen-Tian</au><au>Liu, Jian-Ping</au><au>Wei, Wan-Lin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The effects of tanshinone IIA on hypoxia/reoxygenation-induced myocardial microvascular endothelial cell apoptosis in rats via the JAK2/STAT3 signaling pathway</atitle><jtitle>Biomedicine &amp; pharmacotherapy</jtitle><date>2016-10-01</date><risdate>2016</risdate><volume>83</volume><spage>1116</spage><epage>1126</epage><pages>1116-1126</pages><issn>0753-3322</issn><abstract>Abstract Objective This study aims to investigate the effects of tanshinone IIA on hypoxia/reoxygenation (H/R)-induced myocardial microvascular endothelial cell (MMEC) apoptosis in rats. Methods MMECs from 10-days aged rats were isolated, cultured and identified, which were then divided into following groups: control group, control + tanshinone IIA (50 μM) group, H/R model group, H/R + tanshinone IIA (5 μM) group, H/R + tanshinone IIA (50 μM) pre-treatment group, H/R + AG490 (50 μM) pre-treatment group and H/R + AG490 (50 μM) + tanshinone IIA (50 μM) pre-treatment group. MTT assay, TUNEL staining and flow cytometry were used to measure the cellular viability and apoptosis. Western-blot were performed to detect protein expressions in JAK2/STAT3 signaling pathway. Results Compared with control group, H/R group showed decreased cell viability, increased apoptosis rate, increased proportions of cells into G0/G1 phase, decreased proportions of cells in S phase and G2/M phase, as well as up-regulated expressions of JAK2, STAT3, p53, Bax, Caspase-3, pJAK2 and pSTAT3, and down-regulated Bcl-2 expression (all P &lt; 0.05). Compared with H/R group, H/R + tanshinone IIA (5 μM) group, H/R + tanshinone IIA (50 μM) group H/R + AG490 (50 μM) group and H/R + AG490 (50 μM) + tanshinone IIA (50 μM) group had increased cell viability, decreased apoptosis rate, reduced proportions of cells into G0/G1 phase, elevated proportions of cells in S phase and G2/M phase, as well as down-regulated expressions of JAK2, STAT3, p53, Bax, Caspase-3, pJAK2 and pSTAT3, elevated expression of Bcl-2 (all P &lt; 0.05). The most remarkable changes were observed in H/R + AG490 (50 μM) + tanshinone IIA (50 μM) group. Conclusion Tanshinone IIA may attenuate H/R-induced MMEC apoptosis in rats by inhibiting the JAK2/STAT3 signaling pathway and regulating the expressions of p53, Bax, Caspase-3 and Bcl-2, which may provide a protective effect of tanshinone IIA for MMECs.</abstract><doi>10.1016/j.biopha.2016.07.054</doi><tpages>11</tpages></addata></record>
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title The effects of tanshinone IIA on hypoxia/reoxygenation-induced myocardial microvascular endothelial cell apoptosis in rats via the JAK2/STAT3 signaling pathway
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