本文關鍵詞： 肥胖 血管周圍脂肪組織 瘦素 血管平滑肌細胞　出處：《中華高血壓雜志》2017年03期 　論文類型：期刊論文

【摘要】：目的探討血管周圍脂肪組織來源的瘦素對血管平滑肌細胞(VSMC)增殖的作用及其可能機制。方法 20只8周齡雄性Wistar大鼠隨機分為2組,分別給予高脂飼料及標準大鼠飼料喂養(yǎng),12周后篩選出7只肥胖大鼠作為肥胖組,普食組隨機選取7只作為對照組,每周稱重。喂養(yǎng)12周后,頸動脈插管測得血壓;酶聯免疫吸附試驗(ELISA)檢測大鼠血清瘦素水平;取大鼠降主動脈行HE及Masson染色,比較兩組血管結構改變;Western blot法檢測兩組大鼠血管周圍脂肪組織瘦素和瘦素受體蛋白表達水平。利用大鼠血管周圍脂肪組織制備條件培養(yǎng)基,ELISA法檢測條件培養(yǎng)基中瘦素水平;分別利用條件培養(yǎng)基、瘦素、瘦素拮抗劑(leptin-tA)、細胞外信號調節(jié)激酶(ERK)1/2抑制劑、p38抑制劑等干預大鼠VSMC,四甲基偶氮唑鹽比色法(MTT)檢測細胞增殖情況,Western blot法檢測細胞瘦素、磷酸化ERK1/2(p-ERK1/2)、總ERK1/2(t-ERK1/2)、磷酸化p38(p-p38)、總p38(t-p38)蛋白表達。結果與對照組相比,肥胖組大鼠血清瘦素水平升高;主動脈壁結構紊亂,主動脈中膜厚度[(125.48±20.36)比(80.33±15.62)μm]和中膜厚度/管腔直徑(0.14±0.01比0.08±0.01)增高(均P0.05)。大鼠血管周圍脂肪組織瘦素及瘦素受體蛋白表達增高(均P0.05)。體外實驗發(fā)現,條件培養(yǎng)基(血管周圍脂肪組織細胞培養(yǎng)制成的上清液)瘦素水平明顯升高[(8.34±0.92)比(4.38±0.66)μg/L,P0.05],且高于血清瘦素水平[(8.34±0.92)比(5.85±1.16)μg/L,P0.05];與對照組大鼠血管周圍脂肪組織制備的條件培養(yǎng)基培養(yǎng)的VSMC相比,利用肥胖組大鼠血管周圍脂肪組織制備的條件培養(yǎng)基培養(yǎng)的VSMC增殖顯著增加,ERK1/2、p38磷酸化水平升高(均P0.05);加入瘦素拮抗劑后,細胞ERK1/2及p38磷酸化水平降低(均P0.05);加入瘦素拮抗劑、ERK1/2抑制劑、p38抑制劑后細胞增殖降低(P0.05)。結論血管周圍脂肪組織來源的瘦素可以促進肥胖大鼠VSMC增殖,這種作用可能與ERK1/2和p38信號通路激活有關。
[Abstract]:Objective to investigate the effect of leptin derived from perivascular adipose tissue on proliferation of vascular smooth muscle cells (VSMC) and its possible mechanism. Methods Twenty 8-week-old male Wistar rats were randomly divided into two groups. Seven obese rats were selected as obese group after feeding with high fat diet and standard diet for 12 weeks, and 7 rats in general diet group were randomly selected as control group, weighing weekly. After 12 weeks of feeding, blood pressure was measured by carotid artery intubation. Enzyme linked immunosorbent assay (Elisa) was used to detect the serum leptin level in rats, and the descending aorta of rats was taken for HE and Masson staining. The expression levels of leptin and leptin receptor protein in perivascular adipose tissue of rats were detected by Western blot. Conditioned medium, leptin, leptin-tAn, extracellular signal-regulated kinase ERK1 / 2 inhibitor, p38 inhibitor, were used to interfere with VSMC in rats. The proliferation of VSMCs was detected by tetramethyl azolium colorimetry (MTT). The cell proliferation was detected by Western blot assay. Phosphorylated ERK1 / 2 / 2 p-ERK1 / 2, total ERK1 / 2t-ERK1 / 2, phosphorylated p38 + -p38, total p38-p38) protein expression. Results compared with the control group, the serum leptin level in obese rats increased, and the aortic wall structure was disordered. The thickness of medial membrane of aorta [125.48 鹵20.36] was 80.33 鹵15.62 渭 m, and the thickness of media / diameter of lumen was 0.14 鹵0.01 vs 0.08 鹵0.01 (all P 0.05). The expressions of leptin and leptin receptor protein in perivascular adipose tissue of rats were all increased (P0.05. The leptin level in conditioned medium (supernatant from perivascular adipocyte culture) was significantly increased [8.34 鹵0.92 vs 4.38 鹵0.66 渭 g / L], and higher than serum leptin level [8.34 鹵0.92] vs 5.85 鹵1.16 渭 g / L (P 0.05). The proliferation of VSMC cultured in conditioned culture medium prepared from perivascular adipose tissue of obese rats significantly increased the phosphorylation level of ERK1 / 2 p38 (all P 0.05). The levels of ERK1/2 and p38 phosphorylation were decreased (both P0.05%), and the proliferation of the cells was decreased after the addition of leptin antagonist (P 0.05). Conclusion leptin derived from perivascular adipose tissue can promote the proliferation of VSMC in obese rats. This action may be related to activation of ERK1/2 and p38 signaling pathways.
【作者單位】： 西安交通大學醫(yī)學院第一附屬醫(yī)院心血管內科;西安交通大學醫(yī)學院第一附屬醫(yī)院超聲科;陜西省人民醫(yī)院心血管內三科;山東省立醫(yī)院麻醉科;
【基金】：國家自然科學基金(30871042) 陜西省科學技術研究發(fā)展計劃國際科技合作與交流計劃項目(2012kw-40-01);陜西省科學技術研究發(fā)展計劃自然科學基礎研究計劃項目(2014JM2-8145) 西安市科委攻關項目SF1416(2)
【分類號】：R544.1;R589.2

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