内外湿热对呼吸道病毒感染TLRs介导免疫反应影响的实验与临床研究
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摘要
呼吸道病毒感染为临床常见病和多发病,其中以流感病毒对人类的健康影响最为严重,且近几年发生呈活跃势态。病毒性疾病是否致病与病原体的致病力与人们的免疫力有关,目前药物抗病毒的疗效有限,因此提高和调节免疫能力成了研究重点。TLRs在抗病毒免疫中发挥重要作用,因此以TLRs为靶位,抑制或激活TLRs表达或调控TLRs信号通路,不仅是病毒性疾病新的治疗策略,而且还可作为药物设计和疫苗研制的新靶点。岭南,特别是珠江三角洲地区因气候温暖潮湿、人口稠密成为病毒复制的温床,而其特殊的地理气候及饮食特点,造成其呼吸道病毒感染从中医辨证具有易化热夹湿的特点。我科在以往的临床实践中以蒿芩清胆汤治疗岭南呼吸道病毒湿热证感染取得显著疗效,本实验通过观察岭南地区内外湿热因素(湿热气候、肥甘饮食)对TLRs抗呼吸道病毒免疫反应信号通路的影响,和蒿芩清胆汤及其拆方对此的干预作用,以期探讨湿热证患者在TLRs抗病毒免疫反应方面的特性,也可探讨蒿芩清胆汤治疗病毒性疾病的机制及靶点,为进一步研究中医药治疗病毒性疾病提供实验和临床基础。
目的
本研究以人工气候箱、肥甘饮食模拟岭南地区内外湿热环境,观察内外湿热因素对流感病毒感染小鼠肺组织TLR-7、NF-κB、MyD88的影响,结合临床中上呼吸道病毒感染湿热证患者NF-κB. MyD88表达水平与正常对照组的差异,探讨呼吸道病毒感染湿热证在TLRs介导抗病毒免疫反应方面的特性。实验还暨希望通过蒿芩清胆汤及其拆方对呼吸道病毒感染小鼠肺组织及患者血清TLR-7、NF-κB. MyD88 mRNA表达水平的影响,为上述研究结果提供补充和佐证,同时探讨蒿芩清胆汤治疗病毒性疾病的机制及靶点。
方法
1实验研究：(1)内外湿热因素对小鼠流感病毒性肺炎TLR-7介导免疫反应的影响作用：50只BALB/c小鼠随机分为以下4组：正常对照组、单纯湿热组(湿热环境+肥甘饮食)、湿热模型组(湿热环境+肥甘饮食+病毒感染)、单纯病毒组(病毒感染),观察小鼠症状及体征,检测小鼠肺指数、肺脏病理形态学变化,采用RT-PCR方法检测肺组织流感病毒、TLR-7、NF-κB、MyD88 mRNA水平。(2)蒿芩清胆汤及其拆方对小鼠流感病毒性肺炎湿热证TLR-7介导免疫反应的干预作用：115只BALB/c小鼠按体重随机分为8组：正常对照组、湿热模型组、利巴韦林组、蒿芩清胆汤组、拆方1组、拆方2组、拆方3组、拆方4组,观察小鼠症状及体征,检测小鼠肺指数、肺脏病理形态学变化,采用RT-PCR方法检测肺组织流感病毒、TLR-7、NF-κB、MyD88 mRNA水平。
2临床研究：收集符合西医上呼吸道感染诊断标准及中医湿热证诊断标准者30例为湿热组,健康志愿者随机挑选15位为正常组,用酶联免疫吸附法法检测比较湿热组与正常组血清NF-κB和MyD88表达水平差异、湿热组治疗前后临床症状体征及血清NF-κB和MyD88表达水平差异。
结果
1实验研究
(1)湿热模型组死亡率(33.3%)略高于单纯病毒组(26.7%)。湿热模型组肺指数较单纯病毒组略低,但差异无统计学差异(P＞0.05)。光镜下观察,湿热证模型和单纯病毒均可见细支气管大量炎细胞浸润,肺间质毛细血管扩展充血,肺泡腔内见渗出物。湿热模型组病变程度评分大于单纯病毒组。电镜下观察,湿热模型组病变情况大致同单纯病毒组,但湿热模型肺泡上皮胞浆可见大量脂滴。
(2)内外湿热(肥甘饮食+湿热外环境)与流感病毒感染多重干预的湿热证模型组与单纯病毒组比较,湿热证模型组流感病毒表达水平均值稍高于单纯病毒组,但差异无统计学意义(P>0.05)。
(3)单纯病毒组和湿热证模型组TLR-7、MyD88、NF-κB均值虽较正常组增高,其中三组之间TLR-7、MyD88二者差异无统计学意义,而NF-κB的差异则较大,且有统计学意义；湿热模型组与单纯病毒组比较,前者TLR-7、MyD88. NF-κB三者mRNA表达水平的均值较后者增高,其中NF-κB的增高幅度较大,差异有统计学意义；三者上调幅度不平行。
(4)蒿芩清胆汤及其拆方均能不同程度保护肺组织、抑制流感病毒复制、调低TLR-7、MyD88、NF-κB三者mRNA表达水平,其中蒿芩清胆汤效均最佳。
2临床研究
湿热证患者外周血清MyD88、NF-κB升高,与正常组比较,差异有统计学意义(P<0.05)。经蒿芩清胆汤治疗后,湿热组患者临床症状体征明显改善,外周血清MyD88、NF-κB水平下调,与治疗前比较,差异有显著统计学意义(P<0.01)。
结论
1从实验研究第一节研究结果,我们推测TLR-7、MyD88、NF-κB三者mRNA表达水平均值增高与流感病毒感染相关,但内外湿热因素干预可能引起其较无内外因素干预有较大程度上调,激发大量炎症细胞因子如TNF-α、IL-12等分泌,在吞噬病原体的同时,过度的炎症反应破坏正常组织结构和功能,导致湿热模型组小鼠肺脏病变程度较单纯病毒组重,死亡率也较高。临床研究中,湿热组MyD88、NF-κBmRNA表达水平较正常组增高,且差异有统计学意义,亦为之佐证。
2实验研究中TLR-7、MyD88、NF-κB三者mRNA表达水平上调幅度不平行。考虑有以下几种可能：①TLR-7及MyD88表达水平与病毒毒力相关：本实验感染流感病毒浓度为2LD50,攻击量较小,毒力较弱,故TLR-7二者表达水平变化不大。②TLR-7及MyD88表达水平与病程相关：TLR-7及MyD88于疾病进展过程中消耗,实验取材时间为疾病后期,故二者表达水平较低。③存在其他激活NF-κB表达通道：如在流感病毒引发的炎症反应中,TLR3也通过非MyD88依赖通路—TRIF依赖的信号通路发挥作用,活化NF-κB,导致其上调幅度较大。相关证据需待进一步实验研究证实。
3在实验及临床研究中,蒿芩清胆汤及其拆方具有保护肺脏、抑制流感病毒复制、降低TLR-7、MyD88、NF-κB三者mRNA表达水平的作用,即说明通过清热祛湿、和胃理气可下调上升的TLR-7、MyD88、NF-κB水平,因此,我们推论内外湿热因素干预可能影响TLR-7、MyD88、NF-κB三者mRNA表达水平,解除内外湿热,则能解除干预所带来的一系列病理改变,这或许可为进一步研究蒿芩清胆汤治疗岭南病毒性疾病湿热证机理提供线索及切入点。
Infections of respirovirus are common and frequently-occurring diseases, in which the influenza was most severe and broke out actively recent years. The occurrence of viral deseases is related to viral pathogenicity and people's immunity, but antiviral drugs had limited effects, so it's the point of researches to increase or regulate immunity. TLRs play an important role in antiviral immunity, so TLRs can be not only the new treatment of viral diseases but also new targets of the manufacture of drugs and vaccines. Respirovirus infections in south of Five Ridgs, namely Lingnan, especial the Pearl River Delta, are apt to transmit to heat syndrome and combine damp syndrome because of heat and humid climate, dense population and extraordinary diet. Haoqinqingdan decoction had significant effects on the damp-heat syndrome of Lingnan's respirovirus infections in our past experiences. By observing the effects of exo-endo damp-heat factors on immunological reaction on respirovirus induced by TLRs and the intervention effect of Haoqingqindan decoction and its decomposed recipes, We investigated the characteristics of damp-heat syndrome in immunological reaction induced by TLRs and anti-viral mechanism and targets of Haoqingqindan decoction, and hoped to provide experimental and clinical evidences for further study of Chinese medicine therapy of viral diseases.
Objective
To observe endogenous and exogenous damp-heat factors'effects on the expressions of TLR-7、NF-κB、MyD88 in mice infected by influenza virus through stimulating endogenous and exogenous damp-heat condtions(a richly fatty and sweet diet, heat and humid environment). And to investigate the characteristic of damp-heat syndrome of respirovirus infections in immunological reaction induced by TLRs, while the differences of NF-κB、MyD88 between damp-heat group and control group in clinical experiment were concerned coordinately. We also wanted to offer supplements and evidences for those before by study on the effects of Haoqingqindan decoction and its decomposed recipes on the expression of TLR-7、NF-κB、MyD88 in mouse liver tissue and patients'surum and investigate its mechanism and targets.
Methods
1 Experimental researches:①to study the effect of exo-endo damp-heat factors on immunological reaction on respirovirus induced by TLR-7:40 mice of BALB/c were devided into 4 group randomly (control group, damp-heat group, model group, viral group), then observed the symptom and sign of mice. After executions, lung index and the expression of Influenza virus, TLR-7, NF-κB and MyD88 in lungs of mice were detected by RT-PCR.②to study the intervention effect of Haoqingqindan decoction and its decomposed recipes on immunological reaction on respirovirus induced by TLR-7:115 mice of BALB/c were devided into 8 group randomly (control group, model group, Ribavirin group, HQQD group, decomposed 1 group, decomposed 2 group, decomposed 3 group, decomposed 4 group), then observed the symptom and sign of mice. After executions, lung index and the expression of Influenza virus, TLR-7, NF-κB and MyD88 in lungs of mice were detected by RT-PCR.
2 Clinical research:To collect 30 patients as damp-heat group, who met the diagnosis of Western medicine and damp-heat syndrome of Chinese medicine, while 15 health volunteers were collected randomly as control group. Symptoms and signs and the expression of NF-κB and MyD88 in serum were detected by ELISA before and after treantment.
Results
1 Experimental researches
1) The mortality of model group was a little higher than viral group. The lung index of model group is a little lower than viral group, but the difference wasn't significant (P>0.05). Under light microscope, there were severe inflammatory cell infiltrations in bronchioles, congestion in blood capillaries of pulmonary interstitium and effusion in alveolar space in model group. Pathological changes in model group were more severe than in viral group. Under electron microscope, Pathologic changes in model group was about the same as in viral group, but there were a large number of lipid droplets in alveolar epithelium of model group.
2) The expression of influenza viruses in model group was a little higher than in viral group, but the difference wasn't significant (P>0.05).
3) The mean levels of TLR-7、MyD88、NF-κB in model and viral group was higher than those in control group, but the difference of TLR-7、MyD88 wasn't significant while the difference of NF-κB was significant; The mean levels of TLR-7、MyD88、NF-κB in model group increased to a certain extent than those in viral group, and the difference of NF-κB was significant. The increasing extents of TLR-7、MyD88、NF-κB weren't parallel.
4) Haoqingqindan decoction and its decomposed recipes could inhibit pathological changes, replicate of influenza viruses and decrease the expression of MyD88、NF-κB to a certain extent, in which Haoqingqindan decoction had the best effect.
2 Clinical research
The expression of MyD88、NF-κB in Damp-heat group was higher than in control group, and the difference was significant. After treatment of Haoqingqindan decoction, the expression of MyD88、NF-κB in Damp-heat group increased, and the difference was significant comparing with before treatment. Conclusions
1 Those results of the first experimental research indicated that the increasing of the expression of TLR-7、MyD88、NF-κB is relation to the infections of influenza viruses, but the interventions of exo-endo damp-heat factors also work on it, which to stimulate the secretion of a large number of inflammatory cells factors (such as TNF-α、IL-12 and so on). Then over reaction of inflammatory damaged the normal tissues and functions, which led to severe pathogenetic condition and high mortality. It's also the evidence for those above that the expression of MyD88、NF-κB in damp-heat group increased comparing with control group in clinical test and the difference was significant.
2 In experimental research, the increasing extents of TLR-7、MyD88 NF-κB weren't parallel, we considered that there is likely to be three reasons:①viral virulence:Virulence was weak because of lower viral concentration, so the expression was lower.②course of disease:TLR-7 and MyD88 had been exhausted in later period.③another signal passage:there is another signal passage to stimulate NF-κB,too. Pertinent evidences need further researches.
3 Haoqingqindan decoction and its decomposed recipes could inhibit pathological changes, replicate of influenza viruses and decrease the expression of MyD88、NF-κB to a certain extent, which indicated that the expression of TLR-7、MyD88、NF-κB can be decreased by clearing heat and eliminating dampness, regulating the stomach and Qi. We inferred that the interventions of exo-endo damp-heat factors probably affect the levels of the expression of TLR-7、MyD88、NF-κB. So to remove the exo-endo damp-heat factors can improve the series of pathogenical changes induced by the intervention, which maybe provide a clue or breakthrough point for further study the therapeutic mechanism of Haoqingqingdan decoction on the damp-heat syndrome of viral disease in Lingnan.
目的
本研究以人工气候箱、肥甘饮食模拟岭南地区内外湿热环境,观察内外湿热因素对流感病毒感染小鼠肺组织TLR-7、NF-κB、MyD88的影响,结合临床中上呼吸道病毒感染湿热证患者NF-κB. MyD88表达水平与正常对照组的差异,探讨呼吸道病毒感染湿热证在TLRs介导抗病毒免疫反应方面的特性。实验还暨希望通过蒿芩清胆汤及其拆方对呼吸道病毒感染小鼠肺组织及患者血清TLR-7、NF-κB. MyD88 mRNA表达水平的影响,为上述研究结果提供补充和佐证,同时探讨蒿芩清胆汤治疗病毒性疾病的机制及靶点。
方法
1实验研究：(1)内外湿热因素对小鼠流感病毒性肺炎TLR-7介导免疫反应的影响作用：50只BALB/c小鼠随机分为以下4组：正常对照组、单纯湿热组(湿热环境+肥甘饮食)、湿热模型组(湿热环境+肥甘饮食+病毒感染)、单纯病毒组(病毒感染),观察小鼠症状及体征,检测小鼠肺指数、肺脏病理形态学变化,采用RT-PCR方法检测肺组织流感病毒、TLR-7、NF-κB、MyD88 mRNA水平。(2)蒿芩清胆汤及其拆方对小鼠流感病毒性肺炎湿热证TLR-7介导免疫反应的干预作用：115只BALB/c小鼠按体重随机分为8组：正常对照组、湿热模型组、利巴韦林组、蒿芩清胆汤组、拆方1组、拆方2组、拆方3组、拆方4组,观察小鼠症状及体征,检测小鼠肺指数、肺脏病理形态学变化,采用RT-PCR方法检测肺组织流感病毒、TLR-7、NF-κB、MyD88 mRNA水平。
2临床研究：收集符合西医上呼吸道感染诊断标准及中医湿热证诊断标准者30例为湿热组,健康志愿者随机挑选15位为正常组,用酶联免疫吸附法法检测比较湿热组与正常组血清NF-κB和MyD88表达水平差异、湿热组治疗前后临床症状体征及血清NF-κB和MyD88表达水平差异。
结果
1实验研究
(1)湿热模型组死亡率(33.3%)略高于单纯病毒组(26.7%)。湿热模型组肺指数较单纯病毒组略低,但差异无统计学差异(P＞0.05)。光镜下观察,湿热证模型和单纯病毒均可见细支气管大量炎细胞浸润,肺间质毛细血管扩展充血,肺泡腔内见渗出物。湿热模型组病变程度评分大于单纯病毒组。电镜下观察,湿热模型组病变情况大致同单纯病毒组,但湿热模型肺泡上皮胞浆可见大量脂滴。
(2)内外湿热(肥甘饮食+湿热外环境)与流感病毒感染多重干预的湿热证模型组与单纯病毒组比较,湿热证模型组流感病毒表达水平均值稍高于单纯病毒组,但差异无统计学意义(P>0.05)。
(3)单纯病毒组和湿热证模型组TLR-7、MyD88、NF-κB均值虽较正常组增高,其中三组之间TLR-7、MyD88二者差异无统计学意义,而NF-κB的差异则较大,且有统计学意义；湿热模型组与单纯病毒组比较,前者TLR-7、MyD88. NF-κB三者mRNA表达水平的均值较后者增高,其中NF-κB的增高幅度较大,差异有统计学意义；三者上调幅度不平行。
(4)蒿芩清胆汤及其拆方均能不同程度保护肺组织、抑制流感病毒复制、调低TLR-7、MyD88、NF-κB三者mRNA表达水平,其中蒿芩清胆汤效均最佳。
2临床研究
湿热证患者外周血清MyD88、NF-κB升高,与正常组比较,差异有统计学意义(P<0.05)。经蒿芩清胆汤治疗后,湿热组患者临床症状体征明显改善,外周血清MyD88、NF-κB水平下调,与治疗前比较,差异有显著统计学意义(P<0.01)。
结论
1从实验研究第一节研究结果,我们推测TLR-7、MyD88、NF-κB三者mRNA表达水平均值增高与流感病毒感染相关,但内外湿热因素干预可能引起其较无内外因素干预有较大程度上调,激发大量炎症细胞因子如TNF-α、IL-12等分泌,在吞噬病原体的同时,过度的炎症反应破坏正常组织结构和功能,导致湿热模型组小鼠肺脏病变程度较单纯病毒组重,死亡率也较高。临床研究中,湿热组MyD88、NF-κBmRNA表达水平较正常组增高,且差异有统计学意义,亦为之佐证。
2实验研究中TLR-7、MyD88、NF-κB三者mRNA表达水平上调幅度不平行。考虑有以下几种可能：①TLR-7及MyD88表达水平与病毒毒力相关：本实验感染流感病毒浓度为2LD50,攻击量较小,毒力较弱,故TLR-7二者表达水平变化不大。②TLR-7及MyD88表达水平与病程相关：TLR-7及MyD88于疾病进展过程中消耗,实验取材时间为疾病后期,故二者表达水平较低。③存在其他激活NF-κB表达通道：如在流感病毒引发的炎症反应中,TLR3也通过非MyD88依赖通路—TRIF依赖的信号通路发挥作用,活化NF-κB,导致其上调幅度较大。相关证据需待进一步实验研究证实。
3在实验及临床研究中,蒿芩清胆汤及其拆方具有保护肺脏、抑制流感病毒复制、降低TLR-7、MyD88、NF-κB三者mRNA表达水平的作用,即说明通过清热祛湿、和胃理气可下调上升的TLR-7、MyD88、NF-κB水平,因此,我们推论内外湿热因素干预可能影响TLR-7、MyD88、NF-κB三者mRNA表达水平,解除内外湿热,则能解除干预所带来的一系列病理改变,这或许可为进一步研究蒿芩清胆汤治疗岭南病毒性疾病湿热证机理提供线索及切入点。
Infections of respirovirus are common and frequently-occurring diseases, in which the influenza was most severe and broke out actively recent years. The occurrence of viral deseases is related to viral pathogenicity and people's immunity, but antiviral drugs had limited effects, so it's the point of researches to increase or regulate immunity. TLRs play an important role in antiviral immunity, so TLRs can be not only the new treatment of viral diseases but also new targets of the manufacture of drugs and vaccines. Respirovirus infections in south of Five Ridgs, namely Lingnan, especial the Pearl River Delta, are apt to transmit to heat syndrome and combine damp syndrome because of heat and humid climate, dense population and extraordinary diet. Haoqinqingdan decoction had significant effects on the damp-heat syndrome of Lingnan's respirovirus infections in our past experiences. By observing the effects of exo-endo damp-heat factors on immunological reaction on respirovirus induced by TLRs and the intervention effect of Haoqingqindan decoction and its decomposed recipes, We investigated the characteristics of damp-heat syndrome in immunological reaction induced by TLRs and anti-viral mechanism and targets of Haoqingqindan decoction, and hoped to provide experimental and clinical evidences for further study of Chinese medicine therapy of viral diseases.
Objective
To observe endogenous and exogenous damp-heat factors'effects on the expressions of TLR-7、NF-κB、MyD88 in mice infected by influenza virus through stimulating endogenous and exogenous damp-heat condtions(a richly fatty and sweet diet, heat and humid environment). And to investigate the characteristic of damp-heat syndrome of respirovirus infections in immunological reaction induced by TLRs, while the differences of NF-κB、MyD88 between damp-heat group and control group in clinical experiment were concerned coordinately. We also wanted to offer supplements and evidences for those before by study on the effects of Haoqingqindan decoction and its decomposed recipes on the expression of TLR-7、NF-κB、MyD88 in mouse liver tissue and patients'surum and investigate its mechanism and targets.
Methods
1 Experimental researches:①to study the effect of exo-endo damp-heat factors on immunological reaction on respirovirus induced by TLR-7:40 mice of BALB/c were devided into 4 group randomly (control group, damp-heat group, model group, viral group), then observed the symptom and sign of mice. After executions, lung index and the expression of Influenza virus, TLR-7, NF-κB and MyD88 in lungs of mice were detected by RT-PCR.②to study the intervention effect of Haoqingqindan decoction and its decomposed recipes on immunological reaction on respirovirus induced by TLR-7:115 mice of BALB/c were devided into 8 group randomly (control group, model group, Ribavirin group, HQQD group, decomposed 1 group, decomposed 2 group, decomposed 3 group, decomposed 4 group), then observed the symptom and sign of mice. After executions, lung index and the expression of Influenza virus, TLR-7, NF-κB and MyD88 in lungs of mice were detected by RT-PCR.
2 Clinical research:To collect 30 patients as damp-heat group, who met the diagnosis of Western medicine and damp-heat syndrome of Chinese medicine, while 15 health volunteers were collected randomly as control group. Symptoms and signs and the expression of NF-κB and MyD88 in serum were detected by ELISA before and after treantment.
Results
1 Experimental researches
1) The mortality of model group was a little higher than viral group. The lung index of model group is a little lower than viral group, but the difference wasn't significant (P>0.05). Under light microscope, there were severe inflammatory cell infiltrations in bronchioles, congestion in blood capillaries of pulmonary interstitium and effusion in alveolar space in model group. Pathological changes in model group were more severe than in viral group. Under electron microscope, Pathologic changes in model group was about the same as in viral group, but there were a large number of lipid droplets in alveolar epithelium of model group.
2) The expression of influenza viruses in model group was a little higher than in viral group, but the difference wasn't significant (P>0.05).
3) The mean levels of TLR-7、MyD88、NF-κB in model and viral group was higher than those in control group, but the difference of TLR-7、MyD88 wasn't significant while the difference of NF-κB was significant; The mean levels of TLR-7、MyD88、NF-κB in model group increased to a certain extent than those in viral group, and the difference of NF-κB was significant. The increasing extents of TLR-7、MyD88、NF-κB weren't parallel.
4) Haoqingqindan decoction and its decomposed recipes could inhibit pathological changes, replicate of influenza viruses and decrease the expression of MyD88、NF-κB to a certain extent, in which Haoqingqindan decoction had the best effect.
2 Clinical research
The expression of MyD88、NF-κB in Damp-heat group was higher than in control group, and the difference was significant. After treatment of Haoqingqindan decoction, the expression of MyD88、NF-κB in Damp-heat group increased, and the difference was significant comparing with before treatment. Conclusions
1 Those results of the first experimental research indicated that the increasing of the expression of TLR-7、MyD88、NF-κB is relation to the infections of influenza viruses, but the interventions of exo-endo damp-heat factors also work on it, which to stimulate the secretion of a large number of inflammatory cells factors (such as TNF-α、IL-12 and so on). Then over reaction of inflammatory damaged the normal tissues and functions, which led to severe pathogenetic condition and high mortality. It's also the evidence for those above that the expression of MyD88、NF-κB in damp-heat group increased comparing with control group in clinical test and the difference was significant.
2 In experimental research, the increasing extents of TLR-7、MyD88 NF-κB weren't parallel, we considered that there is likely to be three reasons:①viral virulence:Virulence was weak because of lower viral concentration, so the expression was lower.②course of disease:TLR-7 and MyD88 had been exhausted in later period.③another signal passage:there is another signal passage to stimulate NF-κB,too. Pertinent evidences need further researches.
3 Haoqingqindan decoction and its decomposed recipes could inhibit pathological changes, replicate of influenza viruses and decrease the expression of MyD88、NF-κB to a certain extent, which indicated that the expression of TLR-7、MyD88、NF-κB can be decreased by clearing heat and eliminating dampness, regulating the stomach and Qi. We inferred that the interventions of exo-endo damp-heat factors probably affect the levels of the expression of TLR-7、MyD88、NF-κB. So to remove the exo-endo damp-heat factors can improve the series of pathogenical changes induced by the intervention, which maybe provide a clue or breakthrough point for further study the therapeutic mechanism of Haoqingqingdan decoction on the damp-heat syndrome of viral disease in Lingnan.
引文
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