夏枯草干预实验性自身免疫甲状腺炎Th1/Th2失衡的研究
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摘要
目的观察夏枯草水提取液(PVAE)对实验性自身免疫甲状腺炎(EAT)大鼠炎症及Th1/Th2细胞的干预效果。方法提取PVAE。Lewis大鼠分5组:正常对照(C)组、EAT模型对照(M)组、PVAE预防性治疗(P)组、PVAE低剂量治疗(TL)组和PVAE高剂量治疗(TH)组。试验后取大鼠甲状腺行组织病理学检查,检测大鼠血清促甲状腺激素(TSH),抗甲状腺抗体(TgAb和TPOAb),辅助性T细胞(Th)细胞因子(IFN-γ、IL-4、IL-12和IL-10)水平。结果 (1)各EAT组血浆TSH、TgAb和TPOAb水平均较C组升高,P组TPOAb低于M组(P=0.037)。(2)EAT大鼠Th1类及Th2类表达上调,PVAE干预Th1类上调较M组低,而Th2类较M组高,Th1/Th2比值低于M组。其中IL-12表达和IL-12/IL-10,P组与M组差异有统计学意义(P<0.05)。TL组IL-12水平也低于M组(P=0.018);IL-4水平TH组高于M组(P=0.012);TH组IFN-γ/IL-4低于M组(P=0.018)。(3)TPOAb、IL-10和TgAb依次对TSH有显著性影响(R2=0.868,F=191.389,P<0.001)。结论 PVAE干预可能通过下调EAT大鼠TPOAb、减轻Th1类上调及下调Th1/Th2比值来减轻自身免疫甲状腺炎。
Objective To observe the effects of the aqueous extract isolated from Prunella vulgaris( PVAE) on thyroid inflammation and Th1/Th2 equilibrium in rats with experimental autoimmune thyroiditis( EAT). Methods Lewis rats were randomly divided into 5 groups: normal control group( C),EAT model control group( M),PVAE preventive treatment group( P),low dose of PVAE treatment group( TL) and high dose of PVAE treatment group( TH). Rats were challenged with porcine thyroglobulin( pTg) for immune sensitization except those of group C. Rats of Group P and group TH received 10 g/kg bodyweight per day of crude drugs by ig,and 2. 5 g/( kg·d) in group TL,while those in control groups were given normal saline. The thyroid pathologies,serum autoantibody level and cytokine levels were examined.Results(1)Compared with the group C,both the serum levels of autoantibodies and TSH were higher,while the level of TPOAb in rats of group P were lower than those in group M post treatment( P = 0. 037).(2)The serum cytokine levels produced by T helper 1 and 2 were increased in rats with EAT,PVAE modulated the imbalance of Th1 and Th2 cytokine responses in EAT rats by reducing the levels of Th1 cytokines( IFN-γ and IL-12),but increasing Th2 cytokine( IL-4 and IL-10),while reducing the ratio of Th1/Th2. The serum interleukin-12 concentration and the ratio of IL-12/IL-10 were significantly lower in rats of group P than those in group M after the test( P < 0. 05). Serum IL-12 concentration was also significantly lower in rats of group TL than those in group M after test( P = 0. 018). Additionally the Serum IL-4 concentration was significantly higher in rats of group TH than those in group M after test( P = 0. 021); while the ratio of IFN-γ/IL-4 was lower( P = 0. 018).(3)The correlation analysis showed that the levels of antibodies and T-helper cytokines were all significantly correlated with TSH( P < 0. 001). The level of TPOAb,IL-10 and TgAb may contribute in the modulation of the concentration of TSH( R2= 0. 868,F = 191. 389,P < 0. 001). Conclusion Our research suggesting PVAE as a promising drug for intervention of autoimmune thyroiditis,especially for the prevention treatment of PVAE.
Objective To observe the effects of the aqueous extract isolated from Prunella vulgaris( PVAE) on thyroid inflammation and Th1/Th2 equilibrium in rats with experimental autoimmune thyroiditis( EAT). Methods Lewis rats were randomly divided into 5 groups: normal control group( C),EAT model control group( M),PVAE preventive treatment group( P),low dose of PVAE treatment group( TL) and high dose of PVAE treatment group( TH). Rats were challenged with porcine thyroglobulin( pTg) for immune sensitization except those of group C. Rats of Group P and group TH received 10 g/kg bodyweight per day of crude drugs by ig,and 2. 5 g/( kg·d) in group TL,while those in control groups were given normal saline. The thyroid pathologies,serum autoantibody level and cytokine levels were examined.Results(1)Compared with the group C,both the serum levels of autoantibodies and TSH were higher,while the level of TPOAb in rats of group P were lower than those in group M post treatment( P = 0. 037).(2)The serum cytokine levels produced by T helper 1 and 2 were increased in rats with EAT,PVAE modulated the imbalance of Th1 and Th2 cytokine responses in EAT rats by reducing the levels of Th1 cytokines( IFN-γ and IL-12),but increasing Th2 cytokine( IL-4 and IL-10),while reducing the ratio of Th1/Th2. The serum interleukin-12 concentration and the ratio of IL-12/IL-10 were significantly lower in rats of group P than those in group M after the test( P < 0. 05). Serum IL-12 concentration was also significantly lower in rats of group TL than those in group M after test( P = 0. 018). Additionally the Serum IL-4 concentration was significantly higher in rats of group TH than those in group M after test( P = 0. 021); while the ratio of IFN-γ/IL-4 was lower( P = 0. 018).(3)The correlation analysis showed that the levels of antibodies and T-helper cytokines were all significantly correlated with TSH( P < 0. 001). The level of TPOAb,IL-10 and TgAb may contribute in the modulation of the concentration of TSH( R2= 0. 868,F = 191. 389,P < 0. 001). Conclusion Our research suggesting PVAE as a promising drug for intervention of autoimmune thyroiditis,especially for the prevention treatment of PVAE.
引文
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[2]夏伯候,刘菊妍,李春,等.夏枯草水提液及水提醇沉上清液降血压药效评价[J].中国实验方剂学杂志,2014,20(2):113-116.
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[5]Chen J,Feng X,Huang Q.Modulation of T-Bet and GATA-3 expression in experimental autoimmune thyroiditis rats through ginsenoside treatment[J].Endocr Res,2016,41(1):28-33.
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[7]Zhao X,Zhao J,Hu R,et al.Ruanjian Sanjie decoction exhibits antitumor activity by inducing cell apoptosis in breast cancer[J].Oncol Lett,2017,13(5):3071-3079.
[8]Namgung S,Yoon JJ,Yoon CS,et al.Prunella vulgaris Attenuates Diabetic Renal Injury by Suppressing Glomerular Fibrosis and Inflammation[J].Am J Chin Med,2017,30(3):1-21.
[9]Qu Z,Zhang J,Yang H,et al.Prunella vulgaris L.,an Edible and Medicinal Plant,Attenuates Scopolamine-Induced Memory Impairment in Rats[J].J Agric Food Chem,2017,65(2):291-300.
[10]杨菲,许进,张雪珂,等.夏枯草胶囊治疗单纯甲状腺自身抗体异常的桥本甲状腺炎疗效观察[J].河北中医,2014,36(11):1693-1694.
[11]谢英才,邓碧坚,黄晓君,等.夏枯草口服液对Graves病患者甲状腺大小及促甲状腺受体抗体的影响[J].广东医学,2015,36(2):311-313.
[12]杜丽莉.维生素D缺乏与桥本氏甲状腺炎的相关性研究[J].贵州医药,2014,38(12):1064-1066.
[13]CihákováD,Sharma RB,Fairweather D,et al.Animal models for autoimmune myocarditis and autoimmune thyroiditis[J].Methods Mol Med,2004,102:175-193.
[14]Mikoo's H,Mikoo's M,Obara-Moszyńska M,et al.The role of the immune system and cytokines involved in the pathogenesis of autoimmune thyroid disease(AITD)[J].Endokrynol Pol,2014,65(2):150-155.
[15]Khan FA,Al-Jameil N,Khan MF,et al.Thyroid dysfunction:an autoimmune aspect[J].Int J Clin Exp Med,2015,8(5):6677-6681.
[16]Ruffilli I,Ferrari SM,Colaci M,et al.IP-10 in autoimmune thyroiditis[J].Horm Metab Res,2014,46(9):597-602.
[17]Fallahi P,Ferrari SM,Elia G.Novel Therapies for Thyroid Autoimmune Diseases[J].Expert Rev Clin Pharmacol,2016,9(6):853-861.
[18]Xia N,Chen G,Liu M,et al.Anti-inflammatory effects of luteolin on experimental autoimmune thyroiditis in mice[J].Exp Ther Med,2016,12(6):4049-4054.
[19]Zundler S,Neurath MF.Interleukin-12:Functional activities and implications for disease[J].Cytokine Growth Factor Rev,2015,26(5):559-568.
[20]Guo W,Wang C,Wang X,et al.A novel human truncated IL12rβ1-Fc fusion protein ameliorates experimental autoimmune encephalomyelitis via specific binding of p40 to inhibit Th1 and Th17 cell differentiation[J].Oncotarget,2015,6(30):28539-28555.
[21]Gerenova J,Stanilova S.IL-12B and IL-10 gene polymorphisms in the development of Hashimoto’s thyroiditis[J].Int J Immunogenet,2016,43(6):397-403.
[22]Yu Z,Liu T,Liu S,et al.Interleukin-10 influences susceptibility to experimental autoimmune thyroiditis independently of the H-2 gene[J].Int J Mol Med,2015,35(2):413-424.
[2]夏伯候,刘菊妍,李春,等.夏枯草水提液及水提醇沉上清液降血压药效评价[J].中国实验方剂学杂志,2014,20(2):113-116.
[3]Tan L,Sang ZN,Shen J,et al.Selenium supplementation alleviates autoimmune thyroiditis by regulating expression of Th1/Th2 cytokines[J].Biomed Environ Sci,2013,26(11):920-925.
[4]黄琦,冯晓红,张寅晓,等.人参皂苷对实验性自身免疫性甲状腺炎大鼠Th1/Th2相关细胞因子的影响[J].中医杂志,2013,54(24):2132-2134.
[5]Chen J,Feng X,Huang Q.Modulation of T-Bet and GATA-3 expression in experimental autoimmune thyroiditis rats through ginsenoside treatment[J].Endocr Res,2016,41(1):28-33.
[6]Cui SL,Yu J,Shoujun L.Iodine Intake Increases IP-10 Expression in the Serum and Thyroids of Rats with Experimental Autoimmune Thyroiditis[J].Int J Endocrinol,2014.doi:10.1155/2014/581069.
[7]Zhao X,Zhao J,Hu R,et al.Ruanjian Sanjie decoction exhibits antitumor activity by inducing cell apoptosis in breast cancer[J].Oncol Lett,2017,13(5):3071-3079.
[8]Namgung S,Yoon JJ,Yoon CS,et al.Prunella vulgaris Attenuates Diabetic Renal Injury by Suppressing Glomerular Fibrosis and Inflammation[J].Am J Chin Med,2017,30(3):1-21.
[9]Qu Z,Zhang J,Yang H,et al.Prunella vulgaris L.,an Edible and Medicinal Plant,Attenuates Scopolamine-Induced Memory Impairment in Rats[J].J Agric Food Chem,2017,65(2):291-300.
[10]杨菲,许进,张雪珂,等.夏枯草胶囊治疗单纯甲状腺自身抗体异常的桥本甲状腺炎疗效观察[J].河北中医,2014,36(11):1693-1694.
[11]谢英才,邓碧坚,黄晓君,等.夏枯草口服液对Graves病患者甲状腺大小及促甲状腺受体抗体的影响[J].广东医学,2015,36(2):311-313.
[12]杜丽莉.维生素D缺乏与桥本氏甲状腺炎的相关性研究[J].贵州医药,2014,38(12):1064-1066.
[13]CihákováD,Sharma RB,Fairweather D,et al.Animal models for autoimmune myocarditis and autoimmune thyroiditis[J].Methods Mol Med,2004,102:175-193.
[14]Mikoo's H,Mikoo's M,Obara-Moszyńska M,et al.The role of the immune system and cytokines involved in the pathogenesis of autoimmune thyroid disease(AITD)[J].Endokrynol Pol,2014,65(2):150-155.
[15]Khan FA,Al-Jameil N,Khan MF,et al.Thyroid dysfunction:an autoimmune aspect[J].Int J Clin Exp Med,2015,8(5):6677-6681.
[16]Ruffilli I,Ferrari SM,Colaci M,et al.IP-10 in autoimmune thyroiditis[J].Horm Metab Res,2014,46(9):597-602.
[17]Fallahi P,Ferrari SM,Elia G.Novel Therapies for Thyroid Autoimmune Diseases[J].Expert Rev Clin Pharmacol,2016,9(6):853-861.
[18]Xia N,Chen G,Liu M,et al.Anti-inflammatory effects of luteolin on experimental autoimmune thyroiditis in mice[J].Exp Ther Med,2016,12(6):4049-4054.
[19]Zundler S,Neurath MF.Interleukin-12:Functional activities and implications for disease[J].Cytokine Growth Factor Rev,2015,26(5):559-568.
[20]Guo W,Wang C,Wang X,et al.A novel human truncated IL12rβ1-Fc fusion protein ameliorates experimental autoimmune encephalomyelitis via specific binding of p40 to inhibit Th1 and Th17 cell differentiation[J].Oncotarget,2015,6(30):28539-28555.
[21]Gerenova J,Stanilova S.IL-12B and IL-10 gene polymorphisms in the development of Hashimoto’s thyroiditis[J].Int J Immunogenet,2016,43(6):397-403.
[22]Yu Z,Liu T,Liu S,et al.Interleukin-10 influences susceptibility to experimental autoimmune thyroiditis independently of the H-2 gene[J].Int J Mol Med,2015,35(2):413-424.