青蒿琥酯通过降低TLR4和TLR9mRNA表达保护大肠杆菌脓毒症模型小鼠

目的：观察抗疟药青蒿琥酯对脓毒症模型小鼠的保护作用，探讨其保护作用可能的机制。方法：采用热灭活大肠杆菌建立脓毒症小鼠模型，观察青蒿琥酯对小鼠生存率的影响；采用ELISA法和鲎试剂动态浊度法在体研究青蒿琥酯对脓毒症小鼠血清TNF-α及内毒素水平的影响；采用小鼠腹腔巨噬细胞和RAW264．7细胞从离体水平观察青蒿琥酯对不同致炎因子LPS、CpG ODN和热灭活大肠杆菌诱导细胞因子TNF-α和IL-6释放的影响；采用生物传感器技术、流式细胞技术及RT-PCR分别研究青蒿琥酯与LPS和cpG ODN的直接结合、对细胞表面结合及内吞及TLR4和TLR9mRNA表达的影响。结果：青蒿琥酯对热灭活大肠杆菌脓毒症小鼠具有明显保护作用，可明显降低血清TNF-α及内毒素水平；青蒿琥酯在体外不能直接中和或结合LPS和cpGODN，但可抑制抑制热灭活大肠杆菌、LPS和CpG ODNl826诱导的促炎细胞因子TNF-α、IL-6的释放；青蒿琥酯对细胞内吞或表面结合没有影响，但可抑制热灭活大肠杆菌、LPS和CpG ODNl826诱导的RAW264．7细胞TLR4和TLR9 mRNA高表达。结论：青蒿琥酯可通过降低血清TNF-α释放及内毒素水平保护大肠杆菌脓毒症模型小鼠，其作用可能与降低TLR4和TLR9 mRNA表达有关。     

内毒素耐受状态小鼠对大肠埃希菌敏感性及促炎细胞因子水平变化的研究

目的:研究内毒素耐受状态对大肠埃希菌的敏感性及促炎细胞因子水平的变化。方法:采用小剂量LPS(1mg/kg)连续腹腔注射5d并在第6天尾静脉注射大剂量LPS(50mg/kg)建立小鼠内毒素耐受模型。观察小鼠7d存活率或采用ELISA法检测注射大剂量LPS后6、12h血清中TNF-α、IL-6水平。然后,采用不同浓度的大肠埃希菌攻击耐受小鼠,观察小鼠7d存活率;或采用血培养方法检测血液中细菌数量,ELISA法检测血清中TNF-α、IL-6水平。结果:大剂量LPS攻击组(攻击组)小鼠存活率为0%,LPS耐受组(耐受组)小鼠存活率为100%;耐受组小鼠血清TNF-α、IL-6水平较攻击组显著降低(P<0.01)。5.0×108 CFU/kg大肠埃希菌可导致正常小鼠100%死亡,但是仅1.0×107 CFU/kg大肠埃希菌就可导致耐受组小鼠100%死亡;耐受组给予大肠埃希菌低、高剂量组小鼠血液中细菌数量远远高于相应的正常小鼠大肠埃希菌低或高剂量组(P<0.01),而血清中TNF-α、IL-6水平则远远低于相应的大肠埃希菌低或高剂量组(P<0.01)。结论:连续腹腔注射小剂量LPS 5d后并在第6天尾静脉注射大剂量LPS可成功建立LPS耐受模型;与正常对照组小鼠比较,较低数量的大肠埃希菌就可导致耐受组小鼠死亡,说明内毒素耐受小鼠对大肠埃希菌的敏感性较正常小鼠明显增高,其机制可能与内毒素耐受后促炎细胞因子水平降低、机体抵抗力降低有关。     

流式细胞术检测巨噬细胞吞噬功能的方法建立

目的:建立用流式细胞术检测小鼠腹腔诱导的巨噬细胞吞噬功能的方法。方法:用贴壁法筛选有活性的巨噬细胞,再与用碳酸盐缓冲液制备的荧光素(FITC)标记的大肠埃希菌混合,37℃孵育,每10min取少量固定后加EB染巨噬细胞核,用流式细胞仪检测,计算巨噬细胞对大肠埃希菌的吞噬率。结果:FITC能够有效标记大肠埃希菌;小鼠腹腔诱导的巨噬细胞能够吞噬大肠埃希菌,并且在30min时达到最大峰值。结论:用流式细胞术检测小鼠巨噬细胞吞噬FITC标记大肠埃希菌是测定巨噬细胞吞噬功能简便、快速和重复性好的定量方法。     

青蒿琥酯对小鼠免疫功能的影响(英文)

目的:研究青蒿琥酯对小鼠免疫功能的影响. 方法:溶血素含量用分光光度法测定,血清IgG和C3含量用单向免疫扩散法测定,淋巴细胞转化率、巨噬细胞吞噬百分率和吞噬指数镜检计数.结果:青蒿琥酯im 75 mg kg~(-1) bidfor 5—7d能降低SRBC致敏小鼠血清溶血素和IgG的含量,抑制抗体生成,但增加疟鼠补体C3的含量.青蒿琥酯能促进PHA诱导的小鼠体内淋巴细胞转化,能提高DNFB所致的迟发型超敏反应,并减少腹腔巨噬细胞的吞噬百分率和吞噬指数.结论:青蒿琥酯对体液免疫有抑制作用,但对细胞免疫有促进作用.     

青蒿琥酯对人大肠癌Lovo细胞侵袭影响的初步研究

目的观察青蒿琥酯对大肠癌细胞的侵袭作用,并探讨其作用机制。方法采用不同浓度的青蒿琥酯(20、80、160μmol·L-1)作用于人大肠癌Lovo细胞,软琼脂集落形成实验检测青蒿琥酯对Lovo细胞锚着不依赖性增殖的影响;Transwell侵袭实验检测其对Lovo细胞侵袭的影响;Western blot方法分别检测Lovo细胞内HMGB1和MMP-2蛋白质水平的表达情况。结果青蒿琥酯能有效抑制Lovo细胞的增殖和侵袭能力,且呈剂量依赖性(P<0.01)。与对照组相比,不同浓度青蒿琥酯处理组HMGB1和MMP-2蛋白表达逐渐减少,差异有统计学意义(P<0.05)。结论青蒿琥酯可明显抑制大肠癌Lovo细胞侵袭,其机制可能与抑制HMGB1蛋白,下调MMP-2表达有关。     

亚抑菌量多粘菌素B在大肠埃希氏菌和白色念珠菌混合感染小鼠中的作用

探讨亚抑菌量多粘菌素B对大肠埃希氏菌和白色念珠菌混合感染小鼠病情的影响。建立小鼠大肠埃希氏菌、白色念珠菌单独及混合感染模型，以亚抑菌量多粘菌素B拮抗内毒素活性，观察各组小鼠死亡率、血浆内毒素水平，肺组织中白色念珠菌菌落数及中性粒细胞杀菌能力。结果：大肠埃希氏菌和白色念珠菌混合感染组小鼠死亡率明显高于各自单独感染组（P＜0．05）；大肠埃希氏菌和白色念珠菌混合感染组24h后血浆内毒素水平明显高于大肠埃希氏菌单独感染组（P＜0．01）；大肠埃希氏菌和白色念珠菌混合感染组24h和48h后白色念珠菌菌落数明显高于白色念珠菌单独感染组（P＜0．01）；大肠埃希氏菌和白色念珠菌混合感染组小鼠中性粒细胞杀菌能力明显低于两者单独感染组（P＜0．01）；亚抑菌量多粘菌素B能明显降低混合感染组小鼠死亡率、血浆内毒素水平及肺组织中菌落数，并能增强混合感染组小鼠中性粒细胞杀菌功能（P＜0．05）。结论：亚抑菌量多粘菌量B可改善大肠埃希氏菌和白色念珠菌混合感染小鼠病情。     

青蒿琥酯对脂多糖诱导人结肠上皮细胞炎症反应影响的分子机制研究

目的探讨青蒿琥酯对脂多糖诱导人结肠上皮细胞炎症反应的影响,并研究青蒿琥酯对人结肠上皮细胞炎症治疗作用的可能机制。方法体外原代培养人结肠上皮细胞,并分为空白对照组,LPS诱导组,青蒿琥酯低、中、高剂量组,CCK-8法检测青蒿琥酯对人结肠细胞增殖的影响,ELISA法检测青蒿琥酯对人结肠上皮细胞分泌IL-6和TNF-α炎症因子的影响,Western blot检测青蒿琥酯对Traf6/p65信号通路的影响。结果与LPS诱导组相比,青蒿琥酯能显著改善LPS对人结肠上皮细胞增殖的抑制作用(P<0.05);与LPS诱导组相比,各剂量青蒿琥酯均显著降低了人结肠上皮细胞分泌的IL-6和TNF-α水平(P<0.05);免疫印迹法检测发现,各剂量青蒿琥酯组相对LPS诱导组细胞中Traf6和p-p65表达水平明显降低(P<0.05)。结论青蒿琥酯可抑制人结肠上皮细胞炎症反应,进而改善炎症对细胞增殖的抑制作用,其作用机制可能与下调Traf6/p65信号通路活化有关。     

青蒿琥酯对雨蛙素联合脂多糖致急性胰腺炎模型小鼠的治疗作用

目的：明确青蒿琥酯对急性胰腺炎模型小鼠的治疗作用。方法：昆明种小鼠60只,雌雄各半,随机分为正常组、模型组和治疗组,治疗组又分为三个浓度治疗组,即共5组,每组12只。造模方法为：使用雨蛙素（100 μg/kg）连续6次腹腔注射小鼠,每次间隔1 h;最后一次注射雨蛙素后,腹腔注射LPS（10 mg/kg）。治疗组在造模后0 h和4 h肌肉注射不同浓度的青蒿琥酯,于第一次给药后18 h,眼眶取血,测定血清淀粉酶;脱臼处死小鼠,取胰腺组织,进行胰腺组织学观察及组织病理学评分;测定组织脂肪酶、胰蛋白酶以及超氧化物歧化酶的含量。结果：与模型组相比,青蒿琥酯治疗组的胰腺组织病变情况明显减弱,胰腺系数、血清淀粉酶、组织脂肪酶和胰蛋白酶的活力都明显降低（P〈0.05或P〈0.01）,组织超氧化物歧化酶的活力明显升高（P〈0.05或P〈0.01）。结论：青蒿琥酯对急性胰腺炎模型小鼠具有明显的治疗作用,值得继续深入研究。     

青蒿琥酯及其与放疗联用对CNE细胞的作用

目的研究青蒿琥酯及其与放疗联用对鼻咽癌CNE细胞增殖和凋亡的影响。方法采用细胞集落计数法和原位末端标记（TUNEL）法,测定单用青蒿琥酯及其与放疗联用对CNE细胞增殖的抑制作用和对凋亡的诱导。结果青蒿琥酯能够抑制CNE细胞增殖,并呈现明显的剂量效应,药物浓度2．5～50μg／ml的细胞存活率为15．75％～93．64％。青蒿琥酯可诱导CNE细胞凋亡,高浓度组（10μg／ml）作用比低浓度组（5μg／ml）强（P〈0．05）。当青蒿琥酯与放疗联用时作用更为明显,联用组的作用效果均优于单用青蒿琥酯组或单纯放疗组。结论青蒿琥酯对CNE细胞增殖有明显的抑制和诱导凋亡作用,且和放疗联用作用更强。     

青蒿琥酯对类风湿关节炎滑膜细胞TNF-α分泌的抑制作用及其机制研究

目的研究青蒿素衍生物青蒿琥酯对类风湿关节炎(RA)滑膜细胞(FLS)分泌肿瘤坏死因子(TNF)-α的影响,并进一步探讨其机制。方法来自活动性RA患者的FLS用脂多糖(LPS)刺激和青蒿琥酯处理,TNF-α水平用酶联免疫吸附试验(ELISA)测定,核因子(NF)-κB活性检测采用电泳迁移率改变试验(EMSA)。结果青蒿琥酯显著抑制LPS诱导的TNF-α分泌,并且呈剂量依赖性。青蒿琥酯对LPS刺激的NF-κB活化有明显抑制作用,NF-κB抑制剂二硫代氨基吡咯烷(PDTC)亦显著抑制LPS刺激的滑膜细胞分泌TNF-α。结论青蒿琥酯通过调节NF-κB活性抑制LPS诱导的RA滑膜细胞分泌TNF-α,提示青蒿琥酯可能具有抑制RA滑膜炎症的作用。     

Artesunate in combination with oxacillin protect sepsis model mice challenged with lethal live methicillin-resistant Staphylococcus aureus (MRSA) via its inhibition on proinflammatory cytokines release and enhancement on antibacterial activity of oxacillin

Sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) has worse outcome because of multiresistance to a large group of antibiotics, which may lead to death from septic shock. In the present study, we firstly found that artesunate in combination with oxacillin was capable of protecting mice challenged with live MRSA WHO-2 (WHO-2) and the protection was related to the reduced TNF-α and IL-6 levels and decreased bacterial load. Based on above results, artesunate was further investigated from two aspects in vitro, anti-inflammation effect and antibacterial enhancement effect on antibiotics. Artesunate not only inhibited TNF-α and IL-6 release but also inhibited mRNA and protein expressions of TLR2 and Nod2, two important receptors, in murine peritoneal macrophages stimulated with heat-killed WHO-2, further demonstrating anti-inflammatory effect of artesunate was related to the inhibition of TLR2- and Nod2-mediated proinflammatory cytokines. Significantly, artesunate enhanced antibacterial activity of oxacillin and ampicillin not levofloxacin against WHO-2 and a clinical MRSA strain; the fractional inhibitory concentration indexes were lower than 0.5. Further, artesunate possessed moderate affinity for penicillin-binding protein 2a (PBP2a) and reduced the mecA mRNA expression up-regulated by oxacillin, suggesting that artesunate's enhancement on antibacterial activity of β-lactams was related to the inhibition of PBP2a and down-regulation of mecA mRNA expression. In conclusion, our results demonstrated that artesunate in combination with oxacillin protected mice challenged with lethal live MRSA via its inhibition on proinflammatory cytokines release and enhancement on antibacterial activity of oxacillin. Artesunate could be further investigated as a candidate drug for MRSA sepsis.     

Antimalarial artesunate protects sepsis model mice against heat-killed Escherichia coli challenge by decreasing TLR4, TLR9 mRNA expressions and transcription factor NF-kappa B activation

Bacterial DNA (bDNA) and lipopolysaccharide (LPS) are potent activators of immune cells such as monocytes and macrophages, which contribute to systemic inflammatory response syndrome (SIRS) and sepsis. Unfortunately, many experimental inflammatory antagonist-based therapies have failed in sepsis trials, and currently there is only one adjuvant therapy in clinical use, e.g. activated protein C. Artesunate (AS), a water-soluble derivative of dihydroartemisinin, has recently been demonstrated to protect against LPS-induced human umbilical vein endothelial cell (HUVEC) activation and injury by inhibiting tumor necrosis factor-alpha (TNF-alpha) mRNA expression. In the present study, heat-killed Escherichia coli was used to induce sepsis in the animal models. We observed that AS could protect mice against a lethal challenge with heat-killed E. coli in a dose-dependent manner. This protection was associated with reductions in serum TNF-alpha and measurable endotoxin levels. In addition, the treatment of murine peritoneal macrophage cells with AS strongly inhibited the release of TNF-alpha and IL-6 induced by CpG oligodeoxynucleotide (CpG ODN), LPS, or heat-killed E. coli in a dose-dependent manner. Experiments using affinity sensor technology revealed that AS could not directly bind to CpG ODN or LPS. Moreover, AS could not neutralize LPS in vitro. Further, flow cytometry revealed that AS could not alter the binding of CpG ODN to cell surfaces but could promote CpG ODN accumulation within RAW264.7 cells. Furthermore, AS reduced the expressions of TLR4 and TLR9 mRNA that were stimulated by LPS, CpG ODN, or heat-killed E. coli and inhibited heat killed E. coli-induced NF-kappaB activation. In conclusion, our results demonstrated that AS-mediated protection against a lethal heat-killed E. coli challenge was associated with a reduction in proinflammatory cytokine release and endotoxin levels via a mechanism involving a decrease in TLR4, TLR9 mRNA expression and NF-kappaB activation.     

A synthesized cationic tetradecapeptide from hornet venom kills bacteria and neutralizes lipopolysaccharide in vivo and in vitro

Sepsis is a complex clinical syndrome that results from a harmful host response to infection, in which foreign bacteria and lipopolysaccharide (LPS) are potent activators of different immune cells, including monocytes and macrophages. To date, there are currently few effective adjuvant therapies in clinical use except activated protein C focusing on the coagulation system. Mastoparans (MPs) are wasp venom cationic amphiphilic tetradecapeptides; these are capable of modulating various cellular activities, including stimulation of GTP-binding protein, phospholipase C and can bind to a phospholipid bilayer. Masroparan-1 (MP-1, INLKAIAALAKKLL-NH2), a tetradecapeptide toxin isolated from hornet venom, was synthesized chemically. In this study, Escherichia coli 25922 (E. coli 25922) and LPS were used to induce sepsis in an animal model. We found that MP-1 treatment at 3 mg/kg protected mice from otherwise lethal bacteria and LPS challenges. MP-1 has antibacterial capabilities against Gram-negative and Gram-positive bacteria. Its antibacterial action against E. coli may result from the destruction of bacterial membrane structures. In addition, treatment of murine peritoneal macrophages with MP-1 potently inhibited the respiratory burst. This effect maybe related to an inhibition of NADPH oxidase in the membrane. Furthermore, MP-1, bound with high-affinity to LPS and lipid A with dissociation equilibrium constants of 484 and 456 nM, respectively, and neutralized LPS in a dose-dependent manner. MP-1 also significantly reduced the expression of TLR4, TNF-alpha and IL-6 mRNA and the release of cytokines in LPS-stimulated murine peritoneal macrophages. Our results shows that the MP-1-mediated protection of mice from lethal challenge by live bacteria and LPS was associated with its bactericidal action and inhibition of inflammatory responses by macrophages to both bacteria and LPS (the release of cytokines and reactive oxygen species).     

口服青蒿琥酯对伯氏鼠疟和诺氏猴疟的杀灭效果

目的：研究青芒琥酯口服对伯氏鼠疟和诺氏猴疟的血液开明植体杀灭效果。方法：分别在鼠疟和猴疟模型上采用“４－ｄａｙ试验法”、“２８ｄａｙ”和“７－ｄａｙ”试验法检测了青蒿琥酯和氯喹的药效。结果：口服青蒿琥酯对伯氏鼠疟Ｋ１７３株的抑制效果低于氯喹,但其原虫血症下降５０％、９０％和有的时间比氯喹快１０－１５ｈ,对抗株ＲＣ／Ｋ１７３的疗效优于氯喹,无交叉抗性,Ｉ９０仅为１．４。青蒿琥酯和氯喹对诺氏猴疟在３１     

青蒿琥酯的抗血管生成作用

目的研究青蒿琥酯对血管生成的抑制作用。方法用人脐静脉内皮细胞(HUVEC)的生长、迁移及小管形成实验研究药物的体外抗血管生成作用;用人卵巢癌裸鼠移植瘤模型和免疫组化法研究药物的体内抗血管生成作用。结果青蒿琥酯浓度2.5 μmol·L^-1时,对HUVEC的增殖、迁移和小管形成均有显著的抑制作用;HUVEC 48 h的IC₅₀值为(21±3) μmol·L^-1。在整体实验中,青蒿琥酯50 mg·kg^-1·d^-1即可明显减少肿瘤的血管生成,抑制肿瘤生长;免疫组化结果表明,青蒿琥酯可以抑制VEGF和KDR/flk-1在肿瘤组织中的表达。结论青蒿琥酯有抗血管生成作用,提示该类药物在抗血管生成中有潜在的应用价值。     

青蒿琥酯对人胚肺成纤维细胞Caspase-3表达的影响

目的 研究青蒿琥酯对人胚肺成纤维细胞(human embryonic lung fibroblast,HELF)系HFL-Ⅰ细胞体外生长的影响,为青蒿琥酯抗纤维化提供实验依据.方法 采用CCK-8法检测青蒿琥酯对体外培养的HFL-Ⅰ细胞生长的影响,用流式细胞术测定细胞凋亡率;RT-PCR法测定凋亡相关蛋白Caspase...     

青蒿琥酯对大鼠佐剂性关节炎的抗炎免疫研究

目的研究青蒿琥酯对佐剂性关节炎大鼠的抗炎免疫机制。方法建立佐剂性关节炎大鼠模型,随机分为空白组、AA模型组、甲氨蝶呤阳性药物对照组和青蒿琥酯大、中、小剂量组(20.0,10.0,2.5 mg.kg.d-1),并灌胃给药。ELISA法检测各组对单核细胞趋化因子(MCP-1)、调节活化T细胞表达和分泌因子(RANTES)和肿瘤坏死因子(TNF-α)的影响。结果青蒿琥酯大、中、小剂量组能显著降低血清TNF-α,与模型组比较差异有统计学意义(P<0.05);青蒿琥酯小剂量组与其大、中剂量组或者与甲氨蝶呤组比较差异有统计学意义(P<0.05);青蒿琥酯各剂量组均能显著降低血清中MCP-l和RANTES的表达,与模型组比较差异有统计学意义(P<0.05);而青蒿琥酯小剂量组与大、中剂量组或者与甲氨蝶呤组比较差异有统计学意义(P<0.05)。结论青蒿琥酯抗炎和免疫调节作用可能是与抑制炎症因子相关。     

Chloroquine Inhibits Inducible Nitric Oxide Synthase Expression in Murine Peritoneal Macrophages

Abstract: Induction of inducible nitric oxide synthase in vivo or in vitro in response to stimuli is only temporary. However, chronic localized expression of inducible nitric oxide synthase in certain organs has been associated with the development of autoimmune diseases or chronic inflammatory diseases. Chloroquine is being used as an antiinflammatory drug, and its inhibitory effect on the synthesis of pro-inflammatory cytokines, such as tumour necrosis factor-α and interferon-γ, has been reported. In this study, we examined whether chloroquine could inhibit nitric oxide synthesis in murine peritoneal macrophages stimulated with interferon-γ and lipopolysaccharide. Although prolonged incubation of cells with high concentrations of chloroquine showed some cytotoxicity, the drug itself was not cytotoxic when macrophages were preincubated with chloroquine for 2 hr, washed and stimulated with interferon-γ and lipopolysaccharide in the absence of chloroquine for another 48 hr. The nitric oxide production from stimulated macrophages was markedly reduced by chloroquine in a dose-dependent manner and induction of inducible nitric oxide synthase mRNA was also suppressed by chloroquine pretreatment. These results show that chloroquine inhibits the induction of inducible nitric oxide synthase from interferon-γ and lipopolysaccharide-stimulated macrophages, thereby reducing nitric oxide synthesis.     

青蒿琥酯治疗在马里共和国的恶性疟疾321例

目的 :观察青蒿琥酯对恶性疟疾的疗效。方法 :96 1例恶性疟疾病人随机分成青蒿琥酯组 32 1例 (男性 152例 ,女性 16 9例 ) ,用青蒿琥酯 6 0mg +5%葡萄糖注射液 5mL ,iv ,qd ,首剂加倍 ,疗程 5d ;奎宁 雷琐辛组 32 0例 (男性 140例 ,女性 180例 ) ,用奎宁 雷琐辛 50 0mg + 5%葡萄糖注射液 50 0mL ,iv ,gtt ,qd ,疗程 3d ;氯喹组 32 0例 (男性 143例 ,女性 177例 ) ,用氯喹 50 0mg ,po ,qd ,首剂加倍 ,疗程 3d。各组经 1个疗程治疗后未愈者 ,均继续治疗 1个疗程。结果 :治愈率青蒿琥酯组为 10 0 % ,奎宁 雷琐辛组为 97.5% ,氯喹组为 6 7.2 %。青蒿琥酯组第 2疗程和第 1疗程治愈率分别为 10 0 %和82 .6 % (P <0 .0 1) ,复燃率为 2 .8% ,无不良反应。结论 :青蒿琥酯治疗恶性疟疾安全有效     

异丹叶大黄素和白藜芦醇对小鼠腹腔巨噬细胞白细胞介素6 mRNA表达的影响

目的：观察异丹叶大黄素和白藜芦醇对分别由炎性三肽(fMLP)和钙离子载体A₂₃₁₈₇(A₂₃₁₈₇)诱导的小鼠腹腔巨噬细胞白细胞介素6(interleukin 6, IL-6) mRNA表达水平的影响。方法：用半定量mRNA的RT-PCR。结果：异丹叶大黄素和白藜芦醇在2×10^-6和2×10^-5 mol.L^-1浓度下,均能抑制fMLP和A₂₃₁₈₇诱导的小鼠腹腔巨噬细胞IL-6 mRNA的表达。结论：该2个化合物抑制IL-6活性的作用机制之一是抑制IL-6 mRNA表达。