原花青素對(duì)多囊卵巢綜合征合并動(dòng)脈粥樣硬化模型大鼠的作用

金鉉順，李夢(mèng)京，金 石，張國(guó)杰，元奎昌

·論著·

原花青素對(duì)多囊卵巢綜合征合并動(dòng)脈粥樣硬化模型大鼠的作用

金鉉順，李夢(mèng)京，金 石，張國(guó)杰，元奎昌*

目的 探究原花青素對(duì)多囊卵巢綜合征(PCOS)合并動(dòng)脈粥樣硬化模型大鼠的作用及其機(jī)制。方法 2015年1—10月，采用隨機(jī)數(shù)字表法從20只健康雌性清潔級(jí)SD大鼠中選取15只為建模組，在其頸背部皮下埋置雙氫睪酮(DHT)緩釋片，并且定期更換DHT緩釋片的同時(shí)，給予高脂飼料配方，給予充分的顆粒飼料和水，建立PCOS合并動(dòng)脈粥樣硬化模型大鼠；其余5只大鼠為對(duì)照組，常規(guī)飼養(yǎng)。16周后，分別檢測(cè)兩組大鼠體質(zhì)量、雄激素、瘦素、胰島素水平，光學(xué)顯微鏡下觀察其主動(dòng)脈內(nèi)膜病理情況，以驗(yàn)證PCOS合并動(dòng)脈粥樣硬化模型大鼠成功與否。將建模成功的15只大鼠采用隨機(jī)數(shù)字表法分為模型組、辛伐他汀組、原花青素組，各5只。對(duì)照組與模型組大鼠給予0.9%氯化鈉溶液，辛伐他汀組大鼠給予辛伐他汀片，原花青素組大鼠給予原花青素。治療4周后，檢測(cè)4組大鼠脂代謝指標(biāo)〔總膽固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)〕水平、脂代謝關(guān)鍵基因〔過(guò)氧化物酶體增殖物激活受體γ(PPAR-γ)、3-羥基-3-甲基戊二酰輔酶A還原酶(HMG-CoA還原酶)、ATP結(jié)合盒轉(zhuǎn)運(yùn)子A1(ABCA1)、肝臟X受體α(LXR-α)、法尼醇受體(FXR)〕mRNA表達(dá)水平。結(jié)果 建模組體質(zhì)量、雄激素、瘦素、胰島素水平均低于對(duì)照組(P<0.05)。光學(xué)顯微鏡下觀察大鼠主動(dòng)脈內(nèi)膜病理情況，結(jié)果顯示，與對(duì)照組相比，建模組大鼠主動(dòng)脈內(nèi)膜出現(xiàn)大量粥樣斑塊及膽固醇結(jié)晶。模型組TC、TG、LDL水平高于對(duì)照組(P<0.05)；辛伐他汀組TC、TG、LDL水平低于模型組，HDL水平高于對(duì)照組、模型組(P<0.05)；原花青素組TC、TG、LDL水平低于模型組，TC、LDL水平低于辛伐他汀組，HDL水平高于對(duì)照組、模型組(P<0.05)。模型組PPAR-γ、HMG-CoA還原酶、FXR mRNA表達(dá)水平低于對(duì)照組(P<0.05)；辛伐他汀組PPAR-γ、HMG-CoA還原酶、ABCA1、LXR-α、FXR mRNA表達(dá)水平高于模型組，HMG-CoA還原酶、ABCA1、LXR-α、FXR mRNA表達(dá)水平高于對(duì)照組(P<0.05)；原花青素組PPAR-γ、HMG-CoA還原酶、ABCA1、LXR-α、FXR mRNA表達(dá)水平高于對(duì)照組、模型組，HMG-CoA還原酶mRNA表達(dá)水平高于辛伐他汀組(P<0.05)。4組大鼠主動(dòng)脈內(nèi)膜病理情況：與對(duì)照組相比，模型組大鼠主動(dòng)脈內(nèi)膜出現(xiàn)大量粥樣斑塊及膽固醇結(jié)晶；與模型組相比，辛伐他汀組大鼠主動(dòng)脈內(nèi)膜粥樣斑塊縮小，同時(shí)膽固醇結(jié)晶也減少；與辛伐他汀組相比，原花青素組大鼠主動(dòng)脈內(nèi)膜粥樣斑塊縮小更多，同時(shí)膽固醇結(jié)晶也減少更多。結(jié)論 原花青素可改善PCOS合并動(dòng)脈粥樣硬化模型大鼠脂代謝水平并縮減動(dòng)脈粥樣斑塊。

多囊卵巢綜合征；動(dòng)脈粥樣硬化；原花青素類(lèi)；大鼠；辛伐他汀

金鉉順,李夢(mèng)京,金石,等.原花青素對(duì)多囊卵巢綜合征合并動(dòng)脈粥樣硬化模型大鼠的作用[J].中國(guó)全科醫(yī)學(xué)，2017，20(12)：1463-1468.[www.chinagp.net]

JIN X S,LI M J,JIN S,et al.Effect of procyanidine on rat models of polycystic ovary syndrome complicated with atherosclerosis[J].Chinese General Practice，2017，20(12)：1463-1468.

多囊卵巢綜合征(polycystic ovary syndrome，PCOS)是女性常見(jiàn)的一類(lèi)內(nèi)分泌疾病[1]，以高雄激素血癥及長(zhǎng)期不排卵為主要特征，同時(shí)可伴有痤瘡、月經(jīng)量少、肥胖、代謝紊亂及心血管系統(tǒng)功能紊亂等臨床表現(xiàn)[2-3]。研究統(tǒng)計(jì)，PCOS影響著全世界約7%女性的健康[3]。內(nèi)分泌紊亂是引起機(jī)體代謝失調(diào)的前提。多項(xiàng)研究表明，大多數(shù)PCOS患者存在代謝綜合征，其表現(xiàn)如高血壓、脂代謝異常、肥胖、胰島素抵抗[4]。同時(shí)，PCOS患者心血管疾病患病率明顯增加，成為影響患者預(yù)后的主要因素[4-6]。但PCOS與代謝紊亂是否與心血管疾病相關(guān)，尚未見(jiàn)明確報(bào)道。研究顯示，80%以上的PCOS患者患有心血管疾病，特別是動(dòng)脈粥樣硬化[7]。原花青素是存在于多種植物，如葡萄、藍(lán)莓、紫薯、櫻桃等中的一類(lèi)含多酚羥基的黃酮類(lèi)化合物[8-9]。研究顯示，合理攝入原花青素可起到抗氧化、抑制腫瘤及抗感染等多種作用[10-11]。在動(dòng)脈粥樣硬化的發(fā)生與發(fā)展過(guò)程中，體內(nèi)氧化應(yīng)激增強(qiáng)所致脂質(zhì)過(guò)氧化、泡沫細(xì)胞的激活以及機(jī)體脂質(zhì)代謝異常，是引起動(dòng)脈粥樣斑塊形成的重要因素[12-15]。ZHANG等[16]通過(guò)對(duì)比動(dòng)脈粥樣硬化患者服用原花青素前后動(dòng)脈粥樣斑塊大小、動(dòng)脈內(nèi)膜厚度等指標(biāo)發(fā)現(xiàn)，原花青素可明顯減小動(dòng)脈粥樣斑塊，提示原花青素具有抗動(dòng)脈粥樣硬化的療效。因此，結(jié)合原花青素抗氧化的特性以及脂質(zhì)代謝異常在動(dòng)脈粥樣硬化中扮演的重要角色，本研究觀察原花青素對(duì)PCOS合并動(dòng)脈粥樣硬化模型大鼠的作用及其機(jī)制，以期為探究PCOS病因及其多項(xiàng)并發(fā)癥的病因提供理論指導(dǎo)。

1 材料與方法

1.1 實(shí)驗(yàn)動(dòng)物 2015年1—10月，選取健康雌性清潔級(jí)SD大鼠20只，體質(zhì)量(170±20)g，4周齡，由延邊大學(xué)實(shí)驗(yàn)動(dòng)物中心提供(合格證號(hào)為醫(yī)動(dòng)字第220010016號(hào))。飼養(yǎng)環(huán)境：相對(duì)濕度50%～70%，溫度20～25 ℃，飼料由延邊大學(xué)實(shí)驗(yàn)動(dòng)物中心提供(執(zhí)行標(biāo)準(zhǔn)GB149241994)，動(dòng)物實(shí)驗(yàn)房的合格號(hào)為醫(yī)動(dòng)字第220010015號(hào)。

1.2 藥品與儀器 原花青素購(gòu)于默沙東(中國(guó))有限公司；辛伐他汀片購(gòu)于杭州康泰藥業(yè)有限公司；雄激素、瘦素、胰島素、總膽固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)檢測(cè)試劑盒購(gòu)于上海碧云天生物技術(shù)有限公司；DM2500型光學(xué)顯微鏡、DFA450攝像頭購(gòu)于上海日立電器有限公司。

1.3 研究方法

1.3.1 PCOS合并動(dòng)脈粥樣硬化模型大鼠的建立 采用隨機(jī)數(shù)字表法選取15只大鼠為建模組，在其頸背部皮下埋置雙氫睪酮(DHT)緩釋片(5 mg/90 d，美國(guó)Innovative Research公司，美國(guó)密西西比州Reckelhoff JF生理實(shí)驗(yàn)室贈(zèng)予)，并且在定期更換DHT緩釋片的同時(shí)，給予高脂飼料配方(4%膽固醇+6%花生油+90%基礎(chǔ)飼料，由沈陽(yáng)市于洪區(qū)前民動(dòng)物實(shí)驗(yàn)飼料廠加工成顆粒飼料)，給予充分的顆粒飼料和水。其余5只大鼠為對(duì)照組，常規(guī)飼養(yǎng)。16周后，分別檢測(cè)兩組大鼠體質(zhì)量，按照檢測(cè)試劑盒說(shuō)明書(shū)檢測(cè)雄激素、瘦素、胰島素水平，DM2500型光學(xué)顯微鏡下觀察其主動(dòng)脈內(nèi)膜病理情況，以驗(yàn)證PCOS合并動(dòng)脈粥樣硬化模型大鼠成功與否。

1.3.2 治療方法 將建模成功的15只大鼠采用隨機(jī)數(shù)字表法分為模型組、辛伐他汀組、原花青素組，各5只。對(duì)照組與模型組大鼠灌胃給予10 ml/kg 0.9%氯化鈉溶液，1次/d；辛伐他汀組大鼠灌胃給予4 mg/kg辛伐他汀片，1次/d；原花青素組大鼠灌胃給予50 mg/kg原花青素，1次/d。

1.3.3 檢測(cè)脂代謝指標(biāo)(TC、TG、LDL、HDL)水平 治療4周后，抽取4組大鼠尾靜脈血，分離血漿，采用試劑盒檢測(cè)血漿TC、TG、LDL、HDL水平。

1.3.4 檢測(cè)脂代謝關(guān)鍵基因〔過(guò)氧化物酶體增殖物激活受體γ(PPAR-γ)、3-羥基-3-甲基戊二酰輔酶A還原酶(HMG-CoA還原酶)、ATP結(jié)合盒轉(zhuǎn)運(yùn)子A1(ABCA1)、肝臟X受體α(LXR-α)、法尼醇受體(FXR)〕mRNA表達(dá)水平 治療4周后，斷頸處死各組大鼠，收集頸動(dòng)脈血后分離血漿，采用實(shí)時(shí)熒光定量PCR法檢測(cè)脂代謝關(guān)鍵基因(PPAR-γ、HMG-CoA還原酶、ABCA1、LXR-α、FXR)mRNA表達(dá)水平。PCR反應(yīng)條件：95 ℃預(yù)變性10 min；95 ℃變性15 s，60 ℃退火30 s，72 ℃延伸30 s，共40個(gè)循環(huán)；72 ℃末次延伸5 min。以GAPDH為內(nèi)參，采用2-ΔΔCT法計(jì)算目的基因mRNA表達(dá)水平。

1.3.5 觀察大鼠主動(dòng)脈內(nèi)膜病理情況 采用DM2500型光學(xué)顯微鏡、DFA450攝像頭觀察大鼠主動(dòng)脈內(nèi)膜病理情況。

2 結(jié)果

2.1 PCOS合并動(dòng)脈粥樣硬化大鼠模型的鑒定 建模組體質(zhì)量、雄激素、瘦素、胰島素水平均低于對(duì)照組，差異有統(tǒng)計(jì)學(xué)意義(P<0.05，見(jiàn)表1)。光學(xué)顯微鏡下觀察大鼠主動(dòng)脈內(nèi)膜病理情況，結(jié)果顯示，與對(duì)照組相比，建模組大鼠主動(dòng)脈內(nèi)膜出現(xiàn)大量粥樣斑塊及膽固醇結(jié)晶(見(jiàn)圖1)。

Table 1 Comparison of general data between control group and modeling group

組別只數(shù)體質(zhì)量(g)雄激素(ng/ml)瘦素(ng/ml)胰島素(mU/L)對(duì)照組5196±173.7±0.43.98±0.0129.4±0.9建模組15176±211.8±0.62.14±0.4618.2±0.3t值1.9196.55015.48127.325P值0.071<0.001<0.001<0.001

圖1 光學(xué)顯微鏡下觀察對(duì)照組、建模組主動(dòng)脈內(nèi)膜病理情況(HE染色，×400)

Figure 1 Pathological conditions of the aortic tunica intima in control group and modeling group observed by optical microscopy

2.2 對(duì)照組、模型組、辛伐他汀組、原花青素組脂代謝指標(biāo)水平比較 對(duì)照組、模型組、辛伐他汀組、原花青素組TC、TG、LDL、HDL水平比較，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。其中模型組TC、TG、LDL水平高于對(duì)照組，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)；辛伐他汀組TC、TG、LDL水平低于模型組，HDL水平高于對(duì)照組、模型組，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)；原花青素組TC、TG、LDL水平低于模型組，TC、LDL水平低于辛伐他汀組，HDL水平高于對(duì)照組、模型組，差異有統(tǒng)計(jì)學(xué)意義(P<0.05，見(jiàn)表2)。

Table 2 Comparison of levels of indicators of lipid metabolism in control group,model subgroup,simvastatin subgroup and procyanidine subgroup

組別只數(shù)TCTGLDLHDL對(duì)照組51.52±0.341.24±0.081.16±0.131.23±0.18模型組53.44±0.14a2.98±0.07a2.96±0.32a1.01±0.25辛伐他汀組51.81±0.33b1.62±0.72b1.31±0.32b1.98±0.43ab原花青素組51.13±0.42bc1.02±0.62b0.92±0.23bc2.23±0.51abF值48.52516.68263.48912.824P值<0.001<0.001<0.001<0.001

注：TC=總膽固醇，TG=三酰甘油， LDL=低密度脂蛋白，HDL=高密度脂蛋白；與對(duì)照組比較，aP<0.05；與模型組比較，bP<0.05；與辛伐他汀組比較，cP<0.05

2.3 對(duì)照組、模型組、辛伐他汀組、原花青素組脂代謝關(guān)鍵基因mRNA表達(dá)水平比較 對(duì)照組、模型組、辛伐他汀組、原花青素組PPAR-γ、HMG-CoA還原酶、ABCA1、LXR-α、FXR mRNA表達(dá)水平比較，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。其中模型組PPAR-γ、HMG-CoA還原酶、FXR mRNA表達(dá)水平低于對(duì)照組，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)；辛伐他汀組PPAR-γ、HMG-CoA還原酶、ABCA1、LXR-α、FXR mRNA表達(dá)水平高于模型組，HMG-CoA還原酶、ABCA1、LXR-α、FXR mRNA表達(dá)水平高于對(duì)照組，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)；原花青素組PPAR-γ、HMG-CoA還原酶、ABCA1、LXR-α、FXR mRNA表達(dá)水平高于對(duì)照組、模型組，HMG-CoA還原酶mRNA表達(dá)水平高于辛伐他汀組，差異有統(tǒng)計(jì)學(xué)意義(P<0.05，見(jiàn)表3)。

2.4 對(duì)照組、模型組、辛伐他汀組、原花青素組大鼠主動(dòng)脈內(nèi)膜病理情況 與對(duì)照組相比，模型組大鼠主動(dòng)脈內(nèi)膜出現(xiàn)大量粥樣斑塊及膽固醇結(jié)晶；與模型組相比，辛伐他汀組大鼠主動(dòng)脈內(nèi)膜粥樣斑塊縮小，同時(shí)膽固醇結(jié)晶也減少；與辛伐他汀組相比，原花青素組大鼠主動(dòng)脈內(nèi)膜粥樣斑塊縮小更多，同時(shí)膽固醇結(jié)晶也減少更多(見(jiàn)圖2)。

Table 3 Comparison of mRNA expressions of lipid metabolism-associated genes in control group,model subgroup,simvastatin subgroup and procyanidine subgroup

組別只數(shù)PPAR-γmRNAHMG-CoA還原酶mRNAABCA1mRNALXR-αmRNAFXRmRNA對(duì)照組512.3±3.38.5±1.34.5±1.29.1±2.28.2±1.4模型組55.0±0.8a3.6±0.8a2.5±0.55.5±1.14.2±0.8a辛伐他汀組516.3±4.3b18.5±3.3ab13.9±3.2ab18.3±3.7ab15.3±3.6ab原花青素組518.5±5.3ab27.5±6.1abc17.6±4.4ab22.2±4.9ab17.4±4.2abF值12.04244.75033.61627.68523.098P值<0.001<0.001<0.001<0.001<0.001

注：PPAR-γ=過(guò)氧化物酶體增殖物激活受體γ，HMG-CoA還原酶=3-羥基-3-甲基戊二酰輔酶A還原酶，ABCA1=ATP結(jié)合盒轉(zhuǎn)運(yùn)子A1，LXR-α=肝臟X受體α，F(xiàn)XR=法尼醇受體；與對(duì)照組比較，aP<0.05；與模型組比較，bP<0.05；與辛伐他汀組比較，cP<0.05

圖2 光學(xué)顯微鏡下觀察對(duì)照組、模型組、辛伐他汀組、原花青素組主動(dòng)脈內(nèi)膜病理情況(HE染色，×400)

Figure 2 Pathological conditions of the aortic tunica intima in control group,model subgroup,simvastatin subgroup and procyanidine subgroup observed by optical microscopy

3 討論

PCOS是起源于青春期的生殖內(nèi)分泌紊亂疾病，也是育齡期婦女最常見(jiàn)的內(nèi)分泌疾病，患病率達(dá)5%～10%，在無(wú)排卵性不育的婦女中為50%～60%[17]。PCOS臨床表現(xiàn)多樣，以高雄激素血癥和長(zhǎng)期無(wú)排卵為主要特征，多表現(xiàn)為肥胖、不孕和卵巢囊性增大，且PCOS易引發(fā)多種并發(fā)癥，尤其是心血管疾病，80%以上的PCOS患者患有心血管疾病，特別是動(dòng)脈粥樣硬化[18]。PCOS患者伴有動(dòng)脈粥樣硬化的可能機(jī)制如下[19]：(1)游離脂肪酸的抑制作用減弱，導(dǎo)致LDL和TG合成增加，同時(shí)脂蛋白酯酶和肝脂酶的活性降低，肝臟對(duì)LDL和TG的清除率降低。(2)脂質(zhì)沉積代謝異常，導(dǎo)致脂蛋白酯酶活性受到抑制，從而增加了TG水平，降低了HDL水平，PCOS伴肥胖使血中雄激素、瘦素、胰島素抵抗(IR)水平增加，在其協(xié)同作用下進(jìn)一步加重代謝紊亂。

原花青素是存在于多種植物內(nèi)的一類(lèi)含多酚羥基的黃酮類(lèi)化合物。研究顯示，原花青素具有抗動(dòng)脈粥樣硬化的作用[20]。因此，結(jié)合原花青素抗氧化的特性以及脂質(zhì)代謝異常在動(dòng)脈粥樣硬化中扮演的重要角色，本研究觀察原花青素對(duì)PCOS合并動(dòng)脈粥樣硬化模型大鼠的作用及其機(jī)制，結(jié)果顯示，建模組體質(zhì)量、雄激素、瘦素、胰島素水平均低于對(duì)照組；光學(xué)顯微鏡下觀察大鼠主動(dòng)脈內(nèi)膜病理情況，結(jié)果顯示，與對(duì)照組相比，建模組大鼠主動(dòng)脈內(nèi)膜出現(xiàn)大量粥樣斑塊及膽固醇結(jié)晶。說(shuō)明PCOS合并動(dòng)脈粥樣硬化模型大鼠建模成功。TC、TG、LDL和HDL是評(píng)價(jià)動(dòng)脈粥樣硬化的常見(jiàn)指標(biāo)，TC、TG、LDL水平越高，HDL水平越低，表明動(dòng)脈粥樣硬化程度越嚴(yán)重[18]。模型組TC、TG、LDL水平高于對(duì)照組；辛伐他汀組TC、TG、LDL水平低于模型組，HDL水平高于對(duì)照組、模型組；原花青素組TC、TG、LDL水平低于模型組，TC、LDL水平低于辛伐他汀組，HDL水平高于對(duì)照組、模型組。PPAR-γ、HMG-CoA還原酶、ABCA1、LXR-α、FXR為大鼠脂代謝關(guān)鍵基因，其mRNA能夠啟動(dòng)脂質(zhì)代謝有關(guān)酶的基因轉(zhuǎn)錄，從而促進(jìn)脂肪氧化分解；其mRNA表達(dá)水平越高，越有利于脂肪氧化分解，改善動(dòng)脈粥樣硬化癥狀[21]。本研究結(jié)果顯示，模型組PPAR-γ、HMG-CoA還原酶、FXR mRNA表達(dá)水平低于對(duì)照組；辛伐他汀組PPAR-γ、HMG-CoA還原酶、ABCA1、LXR-α、FXR mRNA表達(dá)水平高于模型組，HMG-CoA還原酶、ABCA1、LXR-α、FXR mRNA表達(dá)水平高于對(duì)照組；原花青素組PPAR-γ、HMG-CoA還原酶、ABCA1、LXR-α、FXR mRNA表達(dá)水平高于對(duì)照組、模型組，HMG-CoA還原酶mRNA表達(dá)水平高于辛伐他汀組。上述結(jié)果證明，原花青素治療PCOS合并動(dòng)脈粥樣硬化效果顯著，甚至強(qiáng)于臨床常用藥辛伐他汀。

由于本研究樣本量小，臨床代表性差，進(jìn)一步的治療效果還需要臨床試驗(yàn)研究；且PCOS合并動(dòng)脈粥樣硬化的發(fā)病機(jī)制需進(jìn)一步明確，因而本研究未能確定原花青素的具體治療機(jī)制，有待進(jìn)一步的研究探討。

綜上所述，原花青素可改善PCOS合并動(dòng)脈粥樣硬化模型大鼠脂代謝水平，并縮減動(dòng)脈粥樣斑塊。

作者貢獻(xiàn)：金鉉順、李夢(mèng)京、金石、張國(guó)杰、元奎昌進(jìn)行文章的構(gòu)思與設(shè)計(jì)、研究的實(shí)施與可行性分析、數(shù)據(jù)收集、數(shù)據(jù)整理、統(tǒng)計(jì)學(xué)處理、結(jié)果的分析與解釋、撰寫(xiě)論文、論文的修訂、英文的修訂，金鉉順負(fù)責(zé)文章的質(zhì)量控制及審校、對(duì)文章整體負(fù)責(zé)、監(jiān)督管理。

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(本文編輯：崔麗紅)

Effect of Procyanidine on Rat Models of Polycystic Ovary Syndrome Complicated with Atherosclerosis

JINXuan-shun,LIMeng-jing,JINShi,ZHANGGuo-jie,YUANKui-chang*

DepartmentofCardiology,YanbianUniversityHospital,Yanji133000,China

*Correspondingauthor:YUANKui-chang,Associatechiefphysician;E-mail:7250599@qq.com

Objective To explore the effect and mechanism of procyanidine on rat models of polycystic ovary syndrome(PCOS) complicated with atherosclerosis.Methods This study was conducted between January and October 2015.For modeling the rats of PCOS complicated with atherosclerosis,we randomly assigned 20 female healthy and clean SD rats to control group(n=5,conventional feeding) and modeling group〔n=15,embedding and regular replacement of dihydrotestosterone(DHT) sustained-release tablets in the subcutaneous tissue of the neck and back and giving enough high-fat food,pellet and water〕.Body weight,androgen,leptin and insulin levels were measured in both groups after 16 weeks of intervention.Aortic tunica intima specimen was taken from both groups and detected by optical microscopy,and the results suggested that the rat models of PCOS complicated with arteriosclerosis were successfully built only in modeling group.Then we randomly divided modeling group into model subgroup,simvastatin subgroup and procyanidine subgroup with 5 rats in each.Both control group and model subgroup were fed with 10 ml/kg 0.9% sodium chloride solution,simvastatin subgroup and procyanidine subgroup were fed with 4 mg/kg simvastatin tablets,50 mg/kg procyanidine,respectively,once a day,for 4 weeks.At the end of this round of intervention,the rat tail vein blood was taken for measuring the levels of lipid metabolism indicators 〔total cholesterol(TC),triacylglycerol(TG),low-density lipoprotein(LDL) and high-density lipoprotein(HDL)〕.Then,all the rats were sacrificed,the carotid artery blood was collected to detect the mRNA expressions of lipid metabolism-associated key genes〔peroxisome proliferator-activated receptor gamma(PPAR-γ),3-hydroxy-3-methyl-glutaryl-CoA(HMG-CoA) reductase,ATP-binding cassette transporter A1(ABCA1),liver X receptor alpha(LXR-α) and farnesoid X receptor(FXR)〕.Results Modeling group had lower body weight,androgen,leptin and insulin levels than control group(P<0.05).There were a lot of atherosclerotic plaques and cholesterol crystals in the aortic tunica intima of modeling group but not in control group found by optical microscopy.TC,TG and LDL levels were higher in model subgroup than in control group(P<0.05);simvastatin subgroup had lower TC,TG and LDL levels but higher HDL level than model subgroup(P<0.05);higher HDL level was noted in simvastatin subgroup than in control group(P<0.05);procyanidine subgroup had lower TC,TG,LDL levels but higher HDL level than model subgroup,lower TC and LDL levels than simvastatin subgroup,and higher HDL level than control group(P<0.05).Compared with control group,model subgroup had lower PPAR-γ,HMG-CoA reductase and FXR mRNA expressions(P<0.05);the mRNA expressions of all the 5 genes were higher in simvastatin subgroup than in model subgroup(P<0.05);HMG-CoA reductase,ABCA1,LXR-α and FXR mRNA expressions were higher in simvastatin subgroup than in control group(P<0.05);procyanidine subgroup had higher PPAR-γ,HMG-CoA reductase,ABCA1,LXR-α,FXR mRNA expressions than both control group and model subgroup,and it had higher HMG-CoA reductase mRNA expression than simvastatin subgroup(P<0.05).Optical microscopy displayed that,much more atherosclerotic plaques and cholesterol crystals appeared in the aortic tunica intima in model subgroup than in control group;atherosclerotic plaques and cholesterol crystals were less in simvastatin subgroup than in model subgroup;procyanidine group showed even less atherosclerotic plaques and cholesterol crystals than simvastatin subgroup.Conclusion Procyanidine could be used to improve the lipid metabolism and reduce the atherosclerotic plaques in rats with PCOS complicated with atherosclerosis.

Polycystic ovary syndrome;Atherosclerosis;Proanthocyanidins;Rats;Simvastatin

國(guó)家自然科學(xué)基金資助項(xiàng)目(81460229)；吉林省教育廳“十二五”科學(xué)技術(shù)研究項(xiàng)目(吉教科合字[2012]第18號(hào))；延邊大學(xué)科技發(fā)展計(jì)劃項(xiàng)目〔延大科合字(2011)第13號(hào)〕

R 711.75 R 543.5

A

10.3969/j.issn.1007-9572.2017.12.011

2016-11-23；

2017-02-21)

133000 吉林省延吉市，延邊大學(xué)附屬醫(yī)院心內(nèi)科

*通信作者：元奎昌，副主任醫(yī)師；E-mail：7250599@qq.com