二仙汤对卵巢切除大鼠棕色脂肪产热相关蛋白表达的影响
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摘要
目的研究二仙汤对卵巢切除大鼠肩胛区棕色脂肪中产热相关蛋白表达的影响。方法 40只雌性SD大鼠随机分为5组,分别为假手术组(SHAM),卵巢切除模型组(OVX),二仙汤低剂量治疗组(EXDL),二仙汤高剂量治疗组(EXDH),雌激素治疗组(E),并分别给予相应的药液连续灌胃给药14周。检测各组大鼠血脂4项;HE染色观察各组大鼠肩胛区棕色脂肪形态学变化;应用Western-blot及q PCR检测各组大鼠肩胛区棕色脂肪中脱偶联蛋白-1(UCP-1)、过氧化物酶体增殖物激活受体γ辅激活因子-1α(PGC-1α)的蛋白及其m RNA的表达水平。结果卵巢切除模型大鼠体质量、腹腔内脂肪质量与假手术组大鼠相比显著增加,卵巢切除大鼠血清总胆固醇水平较假手术组大鼠显著升高;二仙汤治疗后可降低卵巢切除大鼠体质量及腹腔内脂肪质量并降低血清总胆固醇水平。卵巢切除大鼠肩胛区棕色脂肪中UCP-1及PGC-1α的蛋白及其m RNA的表达水平下降,二仙汤治疗后可提高卵巢切除大鼠肩胛区棕色脂肪中UCP-1及PGC-1α的蛋白及其m RNA的表达水平。结论二仙汤可降低卵巢切除大鼠的体质量和腹腔内脂肪的质量并降低血清中总胆固醇的水平,这可能与其提高卵巢切除大鼠肩胛区棕色脂肪中产热相关蛋白UCP-1及PGC-1α的蛋白及其m RNA表达水平有关。
Objective To investigate the effects of Erxian Decoction(ED)on the expression levels of thermogenesisrelated proteins in interscapular brown adipose tissue of ovariectomized rats. Methods Forty female SD rats were randomly divided into sham operation group, ovariectomized group, estrogen group, and low- and high-dose ED groups,which were treated with normal saline,estrogen,ED respectively for 14 weeks. Serum lipids levels were tested. By using HE staining,the morphological features of interscapular brown adipose tissue of rats in each group were observed. The protein and m RNA expression levels of uncoupling protein-1(UCP-1)and peroxisome proliferatoractivated receptor co-activator 1α(PGC-1α)in rat interscapular brown adipose tissue of each group were determined by Western blot and q PCR. Results Compared with sham operation group,rats in ovariectomized group had high body weight, intra-abdominal fat weight and serum cholesterol level. ED treatment was able to decrease body weight,intra-abdominal fat weight and serum cholesterol level in ovariectomized rats. The protein and m RNA levels of UCP-1and PGC-1α in interscapular brown adipose tissue of ovariectomized rats were significantly reduced, and ED treatment could increase the protein and m RNA levels of UCP-1 and PGC-1α in ovariectomized rats. Conclusion ED treatment is effective on decreasing the body weight, interscapular fat weight and serum total cholesterol level in ovariectomized rats. The mechanism is probably associated with the up-regulation of protein and m RNA expression levels of thermogenesis-related proteins UCP-1 and PGC-1α in interscapular brown adipose tissue of ovariectomized rats.
Objective To investigate the effects of Erxian Decoction(ED)on the expression levels of thermogenesisrelated proteins in interscapular brown adipose tissue of ovariectomized rats. Methods Forty female SD rats were randomly divided into sham operation group, ovariectomized group, estrogen group, and low- and high-dose ED groups,which were treated with normal saline,estrogen,ED respectively for 14 weeks. Serum lipids levels were tested. By using HE staining,the morphological features of interscapular brown adipose tissue of rats in each group were observed. The protein and m RNA expression levels of uncoupling protein-1(UCP-1)and peroxisome proliferatoractivated receptor co-activator 1α(PGC-1α)in rat interscapular brown adipose tissue of each group were determined by Western blot and q PCR. Results Compared with sham operation group,rats in ovariectomized group had high body weight, intra-abdominal fat weight and serum cholesterol level. ED treatment was able to decrease body weight,intra-abdominal fat weight and serum cholesterol level in ovariectomized rats. The protein and m RNA levels of UCP-1and PGC-1α in interscapular brown adipose tissue of ovariectomized rats were significantly reduced, and ED treatment could increase the protein and m RNA levels of UCP-1 and PGC-1α in ovariectomized rats. Conclusion ED treatment is effective on decreasing the body weight, interscapular fat weight and serum total cholesterol level in ovariectomized rats. The mechanism is probably associated with the up-regulation of protein and m RNA expression levels of thermogenesis-related proteins UCP-1 and PGC-1α in interscapular brown adipose tissue of ovariectomized rats.
引文
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[18]张清学,杨冬梓,王文军,等.妇女更年期症状调查结果分析[J].中国妇幼保健,2004,11(19):95-98.
[19]陈婉霞,黄国平.更年期综合征中医药治疗进展[J].临床合理用药,2013,6(1):176.
[20]Rogers N H,Perfield J W,Strissel K J,et al.Reduced energy expenditure and increased inflammation are early events in the development ofovariectomy-induced obesity[J].Endocrinology,2009,150(5):2161-2168.
[21]Xu J,Xiang Q,Lin G,et al.Estrogen improved metabolic syndrome through down-regulation of VEGF and HIF-1αto inhibit hypoxia of periaortic and intra-abdominal fat in ovariectomized female rats[J].Molecular Biology Reports,2012,39(8):8177-8185.
[22]尹金磊,赵长普,关素珍.补肾调脾方对女性更年期综合征糖脂代谢的影响[J].中国实验方剂学杂志,2013,19(24):282-286.
[2]Lovejoy J C,Champagne C M,Jonge L D,et al.Increased visceral fat and decreased energy expenditure during the menopausal transition[J].International Journal of Obesity,2008,32(6):949-958.
[3]Poloz Y,Stambolic V.Obesity and cancer,a case for insulin signaling[J].Cell Death and Disease,2015,6(12).
[4]Long M T,Fox C S.The Framingham Heart Study-67 years of discovery in metabolic disease[J].Nature Reviews Endocrinol,2016,12(3):177-183.
[5]Smith K B,Smith M S.Obesity Statistics[J].Primary Care,2016,43(1):121-135.
[6]上海中医学院.中医方剂临床手册[M].上海:上海科技出版社,1982:214.
[7]杨准叶.加味二仙汤治疗更年期综合症60例临床观察[J].四川中医,2011,29(5):91.
[8]娄彦珍,凡艳丽.二仙汤合逍遥散治疗更年期综合征36例[J].实用中医药杂志,2013,29(10):824.
[9]刘宇宁.加味二仙汤治疗绝经后骨质疏松症的疗效观察[J].中国中医基础医学杂志,2012,18(8):886.
[10]薛倩倩,许筱凰,周乐全,等.二仙汤对卵巢切除大鼠胰岛素敏感性的影响[J].中药新药与临床药理,2015,26(5):600-604.
[11]Elattar S,Satyanarayana A.Can Brown Fat Win the Battle Against White Fat?[J].Cell Physiol,2015,230(10):2311-2317.
[12]任莉,赵仓焕.浅谈肥胖从肾论治[J].四川中医,2006,24(6):29-30.
[13]Bartelt A,Bruns O T,Reimer R,et al.Brown adipose tissue activity controls triglyceride clearance[J].Nat Med.2011,17(2):200-205.
[14]Gesta S,Tseng Y H,Kahn C R.Developmental origin of fat:tracking obesity to its source[J].Cell,2007,131(2):242-256.
[15]Nadal-Casellas A,Proenza A M,LladóI,et al.Effects of ovariectomy and 17-βestradiol replacement on rat brown adipose tissue mitochondrial function[J].Steroids,2011,76(10-11):1051-1056.
[16]李博,田瑞霞,杨卫景,等.PGC-1α的功能与代谢病[J].中国生物化学与分子生物学报,2011,27(11):1013-1018.
[17]Liu H M,Huang S Y,Li R M,et al.Andrographolide protects against lipopolysaccharide-induce vascular hyporeactivity by suppressing the expression of inducible nitric oxide in periaortic adipose[J].Journal of Cardiovascular Pharmacology,2013,62(2):154-159.
[18]张清学,杨冬梓,王文军,等.妇女更年期症状调查结果分析[J].中国妇幼保健,2004,11(19):95-98.
[19]陈婉霞,黄国平.更年期综合征中医药治疗进展[J].临床合理用药,2013,6(1):176.
[20]Rogers N H,Perfield J W,Strissel K J,et al.Reduced energy expenditure and increased inflammation are early events in the development ofovariectomy-induced obesity[J].Endocrinology,2009,150(5):2161-2168.
[21]Xu J,Xiang Q,Lin G,et al.Estrogen improved metabolic syndrome through down-regulation of VEGF and HIF-1αto inhibit hypoxia of periaortic and intra-abdominal fat in ovariectomized female rats[J].Molecular Biology Reports,2012,39(8):8177-8185.
[22]尹金磊,赵长普,关素珍.补肾调脾方对女性更年期综合征糖脂代谢的影响[J].中国实验方剂学杂志,2013,19(24):282-286.