慢性乙型肝炎肝郁脾虚、湿热中阻证的证型特点研究
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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.
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
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