摘要
目的:探讨慢性乙型肝炎肝郁脾虚、湿热中阻证的证型特点,为中医辨证提供客观依据。
方法:60例住院及门诊病人,肝郁脾虚型32例,湿热中阻型28例;20例健康对照。采用APAAP法检测外周血T淋巴细胞亚群,双抗体夹心ELISA法检测血清Th1/Th2细胞因子(IL-2、IFN-γ、IL-10)。肝郁脾虚组、湿热中阻组还进行肝功能(A、G、A/G、ALT、AST、TBA)、血清病毒学指标(HBV-M、HBV-DNA)、肝纤维化指标(HA,IIIP、LN)、血型等检测。结果经统计学处理,分析两型间各指标的差异。
结果:(1)肝郁脾虚组CD_3~+、CD_4~+均低于湿热中阻组(P<0.05及P<0.01),肝郁脾虚组CD_4~+低于正常对照组(P<0.05),两组CD_8~+变化不显(P>0.05),CD_4~+/CD_8~+均明显降低(P<0.01及P<0.05),且两组差异显著(P<0.05)。(2)两组OL-2、IFN-γ无明显变化(P>0.05),IL-10肝郁脾虚组较正常对照组明显升高(P<0.05),较湿热中阻组亦升高(P<0.05)。(3)两组肝功能A、G、A/G、ALT、AST无明显差异(P>0.05)。TBA肝郁脾虚型基本正常,湿热中阻型明显升高,两型差异显著(P>0.05)。两型HBV-M、HBV-DNA、HA、IIIP、LN、血型均无明显差异(P>0.05)。
结论:肝郁脾虚型肝损伤较轻,湿热中阻型肝损伤较重。肝郁脾虚型、湿热中阻型慢乙肝患者均存在明显的免疫功能紊乱,CD_4~+/CD_8~+降低,Th1/Th2细胞失衡,且两型之间差异明显,提示两证型免疫水平的差异可作为两证型中医辨证的客观化、量化指标,免疫辨证治疗慢性乙型肝炎成为可能。
Objective:To explore the trait on traditional Chinese medicine (TCM) type of syndrome that stagnation of the liver-Qi and deficiency of the spleen and retention of damp-heat in the interior,provide objective basis for TCM differentiation of symptoms and signs.
Methods: 60 patients ,included stagnation of the liver-Qi and deficiency of the spleen 32 and retention of damp-heat in the interior 28,meanwhile, 20 cases as normal controls.T cell subsets were tested by APAAP method,serum Thl/ Th2 cytokine (1L-2,1FN- Y ,lL-10)Level were tested by ELISA method.At the same timejiver functionjiepatitis B virus(HBV),HBV-DNA,hepatic fibrosis, blood type were tested in patients.
Results:(1)Numbers of CD3+, CD in stagnation of the liver-Qi and deficiency of the spleen were both lower than that in retention of damp-heat in the interior(P<0.05 ,P<0.01),and the numbers of its CD4+also lower than that in controls(P<0.05). compared to controls,numbers of CDs had not distict differences in both of the two groups.while CD, CD, ratio
decreased (P<0.01,P<0.05).Compared to retention of damp-heat in the interior, CD CD ratio decreased distinctively in stagnation of the liver-Qi and deficiency of the spleen(P<0.05).(2)Compared to controls,the levels of IL-2 and IFN- Y in both of the two groups had not distinct differences(P>0.05). Compared to controls and retention of damp-heat in the interior ,the level of IL-10 was higher in stagnation of the liver-Qi and deficiency of the spleen(P<0.05).liver function TBA had distinct difference(P<0.05),butA,G,A/G,ALT,hepatitis B virus(HBV),HBV-DNA, hepatic fibrosis(HA* HIP, LN) and blood type had not distinct difference between the two groups.
Conclusion:Compared to retention of damp-heat in the interior, hepatic injury of stagnation of the liver-Qi and deficiency of the spleen was gentle.Both of them were disorder in immunological function.Ratio of CD// CDg+ decreased, Thl/ Th2 cytokine lost balance.The two groups had distint differences.lt was indicated that the differences of immunity cloud provide objective basis for TCM differentiation of symptoms and signs.Treating chronic hepatitis B according to immunity was reasonable.
引文
1.中国中医药学会内科肝病专业委员会,病毒性肝炎中医辨证标准(试行),中医杂志,1992,(5):39—40
2.中华医学会传染病与寄生虫病学分会、肝病学分会,病毒性肝炎防治法案,中华肝脏病杂志,2000,8(6):324—329
3.连建齐,周永兴,清除乙型肝炎病毒机理的研究进展,传染病信息,2000,13(3):101—103
4. Guidotti LG,Rochford R, Chung J,et al,viral clearance without destrction of infected cells during acute HBV infection[J],Science, 1999,284(5415):825
5. Rehermann B,Floler P, Sidney J, et al,The cyctotoxic T lymphocyte response to multiple hepatitis B virus polymerase eptipes during and acute viral hepatitis, J Exp Med, 1995,181(3): 1047-1058
6. Lchr HF, Krug S,Herr W, et al,Quantitative and functional analysis of core-specific T helper cell and CTL activities in acute and chronic hepatitis B,Liver, 1998,18(6):405-413
7. Barnaba V, Zaccari C,Levrero M,et al,hnmunoregulatory Tcell in HBV-induced chronic liver disease as defined by monoclonal antibodies,Clin Immunol Immunopathol, 1983,26(1):83~85
8.王虹,姚光弼,慢性乙型肝炎T淋巴细胞的肝内浸润与肝损伤的关系,上海免疫学杂志,1993,13(3):140—142
9. Yang PM,Pu IJ,Lai MY, et al, Immunohischemical studies on intrahepatic lymphocyte infiltrates in chronic type B hepatitis with special emphasis on the activation status of lymphocytes, Am J Gastroenterol, 1988,83:948
10. Penna A, Del Prete G,Gavalli A,et al,predominant T-helper lcytokine profile of hepatitis B virus nucleocapsid-specific T cell in acute self-limited hepatitis B,Hepatology, 1997,25(4): 1022
11. Bertoletti A,D'Elios MM,BoniC,et al,Different cytokine profiles of intrahepatic T cells in chronic hepatitis B and Hepatitis C virus
infections, Gastroenterology, 1997,112:193
12.黄明清,刘恒耀,姚正国,等,乙型肝炎患者血清IL—10和IFN—γ水平检测及其意义,中西医结合肝病杂志,2000,10(6):15—16
13.姜荣龙,卢桥生,骆抗先,等,慢性乙型肝炎病毒感染者外周血T辅助细胞1、2型因子的表达,中华传染病杂志,2000,18(1)
14. Milich DR, Peterson DL, Schodel F, et al, Preferential recognition of hepatitis B nucleocapside antigens by Th1 or Th2 cell is epitope and major histocompatibility complex dependent, J Virol, 1995,69(5):2776~2785.
15. Milich DR, Schodel F, Hughes JL,et al,The hepatitis B virus core and e antigens elicit different T_H cell phenotype[J], J Virol, 1997,71(3):2192-2201
16. MILICH DR, Chen MK,Hughes JL,et al,The secreted hepatitis B precore antigen can modulate the immune response to the nucleocapsid:a mechanism for persistence[J],J Immunol, 1998,160(4):2013-2021
17.张剑,许晓东,慢性乙肝免疫状态与中医辨证关系研究,浙江中医杂志,1998,10:444
18.龚远明,张社郎,张仲基,病毒性肝炎的中医分型与免疫的关系,陕西中医,1993,14(7):328
19.崔丽安,温玉焕,张俊富,慢性肝炎患者中医辨证分型与外周血T淋巴细胞亚群及可溶性白细胞介素—2受体的关系,中医杂志,1998,39(8):488—489
20.周虎,周萍,俞庆福,慢性病毒性肝炎T淋巴细胞亚群、免疫球蛋白变化与中医证候关系探讨,江西中医学院学报,2001,13(2):49—50
21.李玲,顾长海,王宇明,等,乙型肝炎患者血清和PDMC培养上清IL—2与IL—10的检测及意义,第三军医大学学报,2001,23(11):1324—1326
22.胡章勇,章廉,文维群,等,慢性乙型肝炎患者T_H1/T_H2细胞因子应答状况,中华微生物和免疫学杂志,2001,21(2):120
23.李晓良,汪承柏,贺江平,慢性乙型肝炎牛医辨证与病理、病毒指标的关系,中西医结合肝病杂志,1996,6(2):4—5,23
24.薛焕德,刘明艳,中医辨证治疗慢性活动性乙型肝炎80例临床观察,中医杂志,1998,39(8):476—478
25.蒋开平,吴寿善,慢性乙型肝炎辨证分型与肝功能变化及肝组织病理类型的关系,新中医,1995,4:44—46
26.辛绍杰,病毒性肝炎肝纤维化的临床与病理研究[J],中华实验与临床病毒杂志,1997,11(3):240.
27.骆群,张导文,血清透明质酸含量测定慢性肝炎及肝硬化与中医分型关系,浙江中西医结合杂志,1997,7(3):136—137
28.李筠,宋为芸,王林杰,等,中医证型与肝炎患者血清肝纤维化指标及肝脏病理关系的研究,新中医,1999,31(2)
29.黄安安,等,乙型肝炎中西医分型与ABO血型关系初探,新中医,1993,25(7):21
30.李振洲,无症状HBsAg携带者的中医治疗,浙江中医杂志,1996,31(9):398—399