中国病理生理杂志
中國病理生理雜誌
중국병리생리잡지
CHINESE JOURNAL OF PATHOPHYSIOLOGY
2010年
3期
440-445
,共6页
盛林%邵利娟%郝琳%徐冬玲%王兴蕾%焦波%潘其兴
盛林%邵利娟%郝琳%徐鼕玲%王興蕾%焦波%潘其興
성림%소리연%학림%서동령%왕흥뢰%초파%반기흥
普罗布可%氧化低密度脂蛋白%硫氧还蛋白1%血红素加氧酶1%细胞外信号调节激酶类%丝裂原活化的蛋白激酶磷酯酶1%平滑肌细胞
普囉佈可%氧化低密度脂蛋白%硫氧還蛋白1%血紅素加氧酶1%細胞外信號調節激酶類%絲裂原活化的蛋白激酶燐酯酶1%平滑肌細胞
보라포가%양화저밀도지단백%류양환단백1%혈홍소가양매1%세포외신호조절격매류%사렬원활화적단백격매린지매1%평활기세포
Probucol%Oxidized low-density lipoproteins%Thioredoxin-1%Heme oxygenase-1%Extracellular signal-regulated kinases%Mitogen-activated protein kinase phosphatase-1%Smooth muscle cells
目的:研究Probucol抑制ox-LDL诱导RASMCs增殖与信号蛋白分子ERK1/2、MKP-1、HO-1和Trx-1表达之间的关系.方法:采用MTT、流式细胞术和Western blotting观察ox-LDL刺激条件下probucol对细胞周期、细胞增殖和凋亡、ERK1/2、MKP-1、HO-1和Trx-1表达的影响.结果:(1)Probucol抑制ox-LDL刺激RASMCs增殖:100 μmol/L probucol+35 mg/L ox-LDL组与35 mg/L ox-LDL组比较,A值下降了34.9%(P<0.01);(2)Probucol通过使RASMCs停滞在G_0/G_1期和诱导细胞凋亡2种方式抑制ox-LDL刺激细胞增殖.(3)ox-LDL显著抑制MKP-1的蛋白表达,与对照组比较下降了60.0%(P<0.01),同时使p-ERK1/2表达增加了34.7%;Probucol使MKP-1蛋白表达显著增加2倍,p-ERK1/2表达降低了15.7%(P<0.01);(4)35 mg/L ox-LDL使细胞内Trx-1蛋白表达下降28.9%(P<0.05),HO-1蛋白表达轻度增加(P<0.05).与ox-LDL组比较,probucol使Trx-1蛋白表达增加了91.6%(P<0.01),HO-1表达增加31.9%(P<0.01).结论:Probucol通过增强MKP-1和HO-1蛋白表达、抑制细胞周期运转和诱导细胞凋亡的机制抑制RASMCs增殖.
目的:研究Probucol抑製ox-LDL誘導RASMCs增殖與信號蛋白分子ERK1/2、MKP-1、HO-1和Trx-1錶達之間的關繫.方法:採用MTT、流式細胞術和Western blotting觀察ox-LDL刺激條件下probucol對細胞週期、細胞增殖和凋亡、ERK1/2、MKP-1、HO-1和Trx-1錶達的影響.結果:(1)Probucol抑製ox-LDL刺激RASMCs增殖:100 μmol/L probucol+35 mg/L ox-LDL組與35 mg/L ox-LDL組比較,A值下降瞭34.9%(P<0.01);(2)Probucol通過使RASMCs停滯在G_0/G_1期和誘導細胞凋亡2種方式抑製ox-LDL刺激細胞增殖.(3)ox-LDL顯著抑製MKP-1的蛋白錶達,與對照組比較下降瞭60.0%(P<0.01),同時使p-ERK1/2錶達增加瞭34.7%;Probucol使MKP-1蛋白錶達顯著增加2倍,p-ERK1/2錶達降低瞭15.7%(P<0.01);(4)35 mg/L ox-LDL使細胞內Trx-1蛋白錶達下降28.9%(P<0.05),HO-1蛋白錶達輕度增加(P<0.05).與ox-LDL組比較,probucol使Trx-1蛋白錶達增加瞭91.6%(P<0.01),HO-1錶達增加31.9%(P<0.01).結論:Probucol通過增彊MKP-1和HO-1蛋白錶達、抑製細胞週期運轉和誘導細胞凋亡的機製抑製RASMCs增殖.
목적:연구Probucol억제ox-LDL유도RASMCs증식여신호단백분자ERK1/2、MKP-1、HO-1화Trx-1표체지간적관계.방법:채용MTT、류식세포술화Western blotting관찰ox-LDL자격조건하probucol대세포주기、세포증식화조망、ERK1/2、MKP-1、HO-1화Trx-1표체적영향.결과:(1)Probucol억제ox-LDL자격RASMCs증식:100 μmol/L probucol+35 mg/L ox-LDL조여35 mg/L ox-LDL조비교,A치하강료34.9%(P<0.01);(2)Probucol통과사RASMCs정체재G_0/G_1기화유도세포조망2충방식억제ox-LDL자격세포증식.(3)ox-LDL현저억제MKP-1적단백표체,여대조조비교하강료60.0%(P<0.01),동시사p-ERK1/2표체증가료34.7%;Probucol사MKP-1단백표체현저증가2배,p-ERK1/2표체강저료15.7%(P<0.01);(4)35 mg/L ox-LDL사세포내Trx-1단백표체하강28.9%(P<0.05),HO-1단백표체경도증가(P<0.05).여ox-LDL조비교,probucol사Trx-1단백표체증가료91.6%(P<0.01),HO-1표체증가31.9%(P<0.01).결론:Probucol통과증강MKP-1화HO-1단백표체、억제세포주기운전화유도세포조망적궤제억제RASMCs증식.
AIM: To investigate the relationships between antiproliferative mechanisms of probucol and protein expressions of signaling molecules ERK1/2, MKP-1, HO-1 and Trx-1 in rat aortic smooth muscle cells (RASMCs) stimulated with ox-LDL. METHODS: The effects of probucol on cell cycle, cell proliferation and the expressions of ERK1/2, MKP-1, HO-1 and Trx-1 in the presence of ox-LDL were observed by means of MTT test, FCM and Western blotting. RESULTS: (1) Probucol significantly inhibited the proliferation of RASMCs stimulated with ox-LDL. A value in 100 μmol/L probucol+35 mg/L ox-LDL group was reduced by 34.9% as compared to ox-LDL group (P<0.01). (2) Probucol protected against ox-LDL-induced RASMCs proliferation through inducing cell growth arrest at G_0/G_1 phase and cell apoptosis. (3) ox-LDL increased the expression of p-ERK1/2 by 34.7% (P<0.01) and decreased MKP-1 by 60.0% (P<0.01), respectively, as compared to control. Probucol attenuated the increase in ox-LDL-stimulated p-ERK1/2 level by 15.7%, but increased MKP-1 expression by 2 times (P<0.01). (4)ox-LDL at concentration of 35 mg/L decreased the intracellular Trx-1 expression by 28.9% (P<0.05), and slightly increased the level of HO-1 expression as compared to control (P<0.05). Probucol enhanced the expression of Trx-1 by 91.6% (P<0.01) and HO-1 by 31.9% (P<0.01), respectively as compared to ox-LDL group. CONCLUSION: Probucol inhibits ox-LDL-stimulated the proliferation of RASMCs through increases in MKP-1/HO-1 expression, suppression of cell cycle progression and induction of cell apoptosis.
