白细胞介素37/Smad3在兔腹主动脉粥样硬化斑块中的表达研究
|
摘要
目的通过检测动脉粥样硬化(AS)斑块中白细胞介素37(IL-37)和Smad3的表达,探讨IL-37/Smad3对AS的影响。方法 20只雄性大白兔按随机数字表法分为对照组(4只,普通饮食)、实验组(8只,高脂饮食)、药物组(8只,高脂饮食+他汀),球囊损伤后建立兔腹主动脉AS模型。实验开始时、6周、12周抽血检查,12周处死动物获取腹主动脉标本,应用血清学、免疫组化、蛋白质印迹法(Western blot)、反转录聚合酶链式反应(RT-PCR)等测定IL-37和Smad3的表达水平。结果 (1)12周处死动物病理显示造模成功,兔腹主动脉形成AS斑块;(2)3组间的血脂、体重和动脉粥样硬化指数在12周有统计学差异(P<0.05);(3)在12周时实验组血清IL-37表达最高,药物组次之,对照组最低,3组间有统计学差异(F=20.76,P<0.05);(4)免疫组化显示实验组的IL-37和Smad3表达最高,药物组次之,对照组最低;(5)Western blot、RT-PCR显示IL-37和Smad3在实验组表达最高,药物组次之,对照组最低,3组间有统计学差异(F=28.56和82.23,91.23和48.87,均为P<0.05),Western blot和RT-PCR均提示IL-37和Smad3呈高度直线相关(r=0.929, 0.942,均为P<0.05)。结论 IL-37和Smad3在AS斑块表达增高,IL-37/Smad3可能参与AS的调节过程,阿托伐他汀可降低IL-37/Smad3的表达。
Objective To investigate the effect of interleukin-37(IL-37)/Smad3 on atherosclerosis by detecting the expression of IL-37 and Smad3 in atherosclerotic plaques. Methods Rabbit abdominal aorta atherosclerosis models were established by balloon injury. 20 male white rabbits were randomly divided into control group(n=4, normal diet), experimental group(n=8, high cholesterol diet), drug group(n=8, high cholesterol diet add statin). Blood samples were taken at the beginning of experiment, 6 weeks and 12 weeks later. At 12 weeks the animals were sacrificed and the abdominal aorta samples were obtained. Immunohistochemistry, Western blot and RT-PCR were used to detect IL-37 and Smad3. Results(1)Animal pathology at 12 weeks showed that the rabbits formed the atherosclerotic plaques in the abdominal aorta successfully;(2)There were significant differences in blood lipid, body weight and atherosclerosis index among the three groups at 12 weeks(all P<0.05);(3)The serum IL-37 in the experimental group was the highest, followed by the drug group, the control group was the lowest at 12 weeks(F=20.76, P<0.05);(4)Immunohistochemistry showed that the expressions of IL-37 and Smad3 in the experimental group was the highest and the control group was the lowest;(5)Western blot, RT-PCR all showed IL-37 and Smad3 in the experimental group was the highest, followed by drug group, the control group was the lowest(F=28.56 and 82.23, 91.23 and 48.87, all P<0.05); IL-37 was linearly correlated with Smad3(r=0.929, 0.942, both P<0.05). Conclusions The expression of IL-37 and Smad3 is increased in atherosclerotic plaque; IL-37/Smad3 may be involved in the regulation of atherosclerosis. Atorvastatin can reduce the expression of IL-37/Smad3 in atherosclerotic plaques.
Objective To investigate the effect of interleukin-37(IL-37)/Smad3 on atherosclerosis by detecting the expression of IL-37 and Smad3 in atherosclerotic plaques. Methods Rabbit abdominal aorta atherosclerosis models were established by balloon injury. 20 male white rabbits were randomly divided into control group(n=4, normal diet), experimental group(n=8, high cholesterol diet), drug group(n=8, high cholesterol diet add statin). Blood samples were taken at the beginning of experiment, 6 weeks and 12 weeks later. At 12 weeks the animals were sacrificed and the abdominal aorta samples were obtained. Immunohistochemistry, Western blot and RT-PCR were used to detect IL-37 and Smad3. Results(1)Animal pathology at 12 weeks showed that the rabbits formed the atherosclerotic plaques in the abdominal aorta successfully;(2)There were significant differences in blood lipid, body weight and atherosclerosis index among the three groups at 12 weeks(all P<0.05);(3)The serum IL-37 in the experimental group was the highest, followed by the drug group, the control group was the lowest at 12 weeks(F=20.76, P<0.05);(4)Immunohistochemistry showed that the expressions of IL-37 and Smad3 in the experimental group was the highest and the control group was the lowest;(5)Western blot, RT-PCR all showed IL-37 and Smad3 in the experimental group was the highest, followed by drug group, the control group was the lowest(F=28.56 and 82.23, 91.23 and 48.87, all P<0.05); IL-37 was linearly correlated with Smad3(r=0.929, 0.942, both P<0.05). Conclusions The expression of IL-37 and Smad3 is increased in atherosclerotic plaque; IL-37/Smad3 may be involved in the regulation of atherosclerosis. Atorvastatin can reduce the expression of IL-37/Smad3 in atherosclerotic plaques.
引文
[1] 李国华,李佳旻.炎症因子与动脉粥样硬化[J].心血管病学进展,2010,31(2):156-158.DOI:10.3969/j.issn.1004-3934.2010.02.002.Li GH,Li JM.Inflammatory factors and atherosclerosis[J].Adv Cardiovasc Dis,2010,31(2):156-158.DOI:10.3969/j.issn.1004-3934.2010.02.002.
[2] 陈少源,贺五一,金健,等.急性冠状动脉综合征患者白细胞介素-37水平变化的研究[J].中国循环杂志,2014,11:871-874.DOI:10.3969/j.issn.1000-3614.2014.11.004.Chen SY,He WY,Jin J,et al.Changes of interleukin-37 levels in patients with acute coronary syndrome [J].Chin Circ J,2014,11:871-874.DOI:10.3969/j.issn.1000-3614.2014.11.004.
[3] 方红城,陈少源,吴保泉,等.血清Legumain在急性冠脉综合征患者中的变化[J].广东医学,2016,37(19):2929-2931.DOI:10.3969/j.issn.1001-9448.2016.19.026.Fang HC,Chen SY,Wu BQ,et al.Changes of serum Legumain in patients with acute coronary syndrome [J].Guangdong Med,2016,37(19):2929-2931.DOI:10.3969/j.issn.1001-9448.2016.19.026.
[4] 李梦媛,杨星九,徐大模,等.IL-37对炎症相关性疾病的抑制作用[J].中国比较医学杂志,2015(12):75-80.DOI:10.3969/j.issn.1671-7856.2015.12.015.Li MY,Yang XJ,Xu DM,et al.Inhibitory effect of IL-37 on inflammatory-related diseases [J].Chin J Comp Med,2015,25(12):75-80.DOI:10.3969/j.issn.1671-7856.2015.12.015.
[5] Liu R,Tang C,Shen A,et al.IL-37 suppresses hepatocellular carcinoma growth by converting pSmad3 signaling from JNK/pSmad3L/c-Myc oncogenic signaling to pSmad3C/P21 tumor-suppressive signaling[J].Oncotarget,2016,7(51):85079-85081.DOI:10.18632/oncotarget.13196.
[6] Mccurdy S,Liu CA,Yap J,et al.Potential role of IL-37 in atherosclerosis[J].Cytokine,2017,23 (3):82-83.DOI:10.1016/j.cyto.2017.09.025.
[7] Song C L,Wang J P,Xue X,et al.Effect of Circular ANRIL on the Inflammatory Response of Vascular Endothelial Cells in a Rat Model of Coronary Atherosclerosis[J].Cell Physiol Biochem,2017,42(3):1202-1205.DOI:10.1159/000478918.
[8] 黄于朗,陈少源,苏又苏.白细胞介素-37与动脉粥样硬化的关系[J].广东医学,2013,34(24):3812-3814.Huang YL,Chen SY,Su YS.The relationship between interleukin-37 and atherosclerosis [J].Guangdong Med,2013,34(24):3812-3814.
[9] Bouali E,Kaabachi W,Hamzaoui A,et al.Interleukin-37 expression is decreased in Behet's disease and is associated with inflammation[J].Immunol Lett,2015,167(2):87-94.DOI:10.1016/j.imlet.2015.08.001.
[10] Ye Z,Wang C,Kijlstra A,et al.A possible role for interleukin 37 in the pathogenesis of Behcet's disease.[J].Curr Mol Med,2014,14(4):18-24.
[11] Boraschi D,Lucchesi D,Hainzl S,et al.IL-37:a new anti-inflammatory cytokine of the IL-1 family[J].Eur Cytokine Netw,2011,22(3):127-128.DOI:10.1684/ecn.2011.0288.
[12] Baetta R,Lento S,Ghilardi S,et al.Atorvastatin reduces long pentraxin 3 expression in vascular cells by inhibiting protein geranylgeranylation[J].Vascul Pharmacol,2015,5(67):38-47.DOI:10.1016/j.vph.2014.11.008.
[13] Mitsios JV,Papathanasiou AI,Goudevenos JA,et al.The antiplatelet and antithrombotic actions of statins[J].Curr Pharm Des,2010,16(34):29-38.
[14] Terkeltaub R.What makes gouty inflammation so variable?[J].BMC Med,2017,15(1):158-159.DOI:10.1186/s12916-017-0922-5.
[2] 陈少源,贺五一,金健,等.急性冠状动脉综合征患者白细胞介素-37水平变化的研究[J].中国循环杂志,2014,11:871-874.DOI:10.3969/j.issn.1000-3614.2014.11.004.Chen SY,He WY,Jin J,et al.Changes of interleukin-37 levels in patients with acute coronary syndrome [J].Chin Circ J,2014,11:871-874.DOI:10.3969/j.issn.1000-3614.2014.11.004.
[3] 方红城,陈少源,吴保泉,等.血清Legumain在急性冠脉综合征患者中的变化[J].广东医学,2016,37(19):2929-2931.DOI:10.3969/j.issn.1001-9448.2016.19.026.Fang HC,Chen SY,Wu BQ,et al.Changes of serum Legumain in patients with acute coronary syndrome [J].Guangdong Med,2016,37(19):2929-2931.DOI:10.3969/j.issn.1001-9448.2016.19.026.
[4] 李梦媛,杨星九,徐大模,等.IL-37对炎症相关性疾病的抑制作用[J].中国比较医学杂志,2015(12):75-80.DOI:10.3969/j.issn.1671-7856.2015.12.015.Li MY,Yang XJ,Xu DM,et al.Inhibitory effect of IL-37 on inflammatory-related diseases [J].Chin J Comp Med,2015,25(12):75-80.DOI:10.3969/j.issn.1671-7856.2015.12.015.
[5] Liu R,Tang C,Shen A,et al.IL-37 suppresses hepatocellular carcinoma growth by converting pSmad3 signaling from JNK/pSmad3L/c-Myc oncogenic signaling to pSmad3C/P21 tumor-suppressive signaling[J].Oncotarget,2016,7(51):85079-85081.DOI:10.18632/oncotarget.13196.
[6] Mccurdy S,Liu CA,Yap J,et al.Potential role of IL-37 in atherosclerosis[J].Cytokine,2017,23 (3):82-83.DOI:10.1016/j.cyto.2017.09.025.
[7] Song C L,Wang J P,Xue X,et al.Effect of Circular ANRIL on the Inflammatory Response of Vascular Endothelial Cells in a Rat Model of Coronary Atherosclerosis[J].Cell Physiol Biochem,2017,42(3):1202-1205.DOI:10.1159/000478918.
[8] 黄于朗,陈少源,苏又苏.白细胞介素-37与动脉粥样硬化的关系[J].广东医学,2013,34(24):3812-3814.Huang YL,Chen SY,Su YS.The relationship between interleukin-37 and atherosclerosis [J].Guangdong Med,2013,34(24):3812-3814.
[9] Bouali E,Kaabachi W,Hamzaoui A,et al.Interleukin-37 expression is decreased in Behet's disease and is associated with inflammation[J].Immunol Lett,2015,167(2):87-94.DOI:10.1016/j.imlet.2015.08.001.
[10] Ye Z,Wang C,Kijlstra A,et al.A possible role for interleukin 37 in the pathogenesis of Behcet's disease.[J].Curr Mol Med,2014,14(4):18-24.
[11] Boraschi D,Lucchesi D,Hainzl S,et al.IL-37:a new anti-inflammatory cytokine of the IL-1 family[J].Eur Cytokine Netw,2011,22(3):127-128.DOI:10.1684/ecn.2011.0288.
[12] Baetta R,Lento S,Ghilardi S,et al.Atorvastatin reduces long pentraxin 3 expression in vascular cells by inhibiting protein geranylgeranylation[J].Vascul Pharmacol,2015,5(67):38-47.DOI:10.1016/j.vph.2014.11.008.
[13] Mitsios JV,Papathanasiou AI,Goudevenos JA,et al.The antiplatelet and antithrombotic actions of statins[J].Curr Pharm Des,2010,16(34):29-38.
[14] Terkeltaub R.What makes gouty inflammation so variable?[J].BMC Med,2017,15(1):158-159.DOI:10.1186/s12916-017-0922-5.