黄芪皂甙对小鼠柯萨奇B3病毒性心肌炎的治疗作用

目的:探讨黄芪皂甙对BALB/c小鼠柯萨奇B3(CVB3)病毒性心肌炎的治疗作用。方法:雄性BALB/c小鼠腹腔接种CVB3,制成急性病毒性心肌炎模型,接种1 h后腹腔内注入黄芪皂甙5.64×10-3 mg/g,1次/d ×7 d,观测小鼠存活率、血浆乳酸脱氢酶(LDH)和谷草转氨酶(GOT)、体温、心肌病理变化和心肌病毒滴度的影响。结果:黄芪皂甙治疗组比病毒感染组存活率明显增高,血浆LDH和GOT明显降低,体温保持正常,心脏质量/体质量值显著降低,心肌病理变化减轻,心肌匀浆病毒滴度降低(P＜0.05)。结论:黄芪皂甙有治疗病毒性心肌炎的作用。     

卡维地洛对柯萨奇病毒B3病毒性心肌炎小鼠的疗效及其抗氧化应激作用

目的观察卡维地洛对柯萨奇病毒B3(CVB3)病毒性心肌炎小鼠的疗效。方法将80只小鼠随机分为3组:正常对照组(n=20),心肌炎组(n=30)与卡维地洛组(n=30),利用BALB/C小鼠感染CVB3建立病毒性心肌炎模型,感染24 h后每天灌胃给予卡维地洛10 mg/kg直至第14天,分别于接种第7天和第14天随机从各组抽取若干只小鼠取血后处死并留取心脏等标本。结果卡维地洛降低病毒性心肌炎小鼠急性期的死亡率,显著减轻心脏病理损伤,显著降低HW/BW(HW=心脏重量,BW=身体重量)比值;小鼠感染CVB3后第7天和第14天体内脂质过氧化物丙二醛(MDA)增高而超氧化物岐化酶(SOD)降低;卡维地洛干预后第7天小鼠心肌与血清中MDA含量显著降低,SOD含量有增加趋势但无统计学意义;干预后第14天SOD含量显著增加,MDA含量显著降低。结论卡维地洛对病毒性心肌炎有保护作用,不仅可以显著减轻感染小鼠的心肌损害,提高生存率,还具有明显抗氧化功效。     

大蒜多糖对病毒性心肌炎小鼠心肌酶的影响

目的 探讨大蒜多糖对实验性病毒性心肌炎小鼠心肌酶的影响。方法 采用BALB/C小鼠腹腔注射柯萨奇病毒B3(CVB3)建立实验性小鼠病毒性心肌炎模型。小鼠随机分为正常对照组、模型组、大蒜多糖I组、大蒜多糖Ⅱ组、大蒜多糖Ⅲ组和黄芪组。注射病毒1小时后给药，连续7天，于第8天处死存活鼠取材。观察小鼠存活率及心肌病理变化，测定血清心肌酶及心肌组织中的病毒滴度。结果 大蒜多糖治疗组与模型组相比小鼠存活率明显增高，心肌组织病理损伤减轻，血清心肌酶含量和心肌组织中病毒滴度明显降低。结论 大蒜多糖对实验性小鼠病毒性心肌炎具有治疗作用。     

柯萨奇B3m病毒感染新生乳鼠致急性病毒性心肌炎模型的研究

目的 探讨制备柯萨奇B3m病毒感染Balb/C新生乳鼠急性病毒性心肌炎模型的实验途径。方法 地柯萨奇B3m亲心肌株病毒进行增毒，滴定TCID50后感染Balb/C新生乳鼠。CVB3m病毒感染组3窝共21只，对照组3窝共20只。感染组每只乳鼠腹腔内接种1000TCID50CVB3m病毒液0.04ml，对照组每只乳鼠腹腔内接种1640维持液0.04ml。观察感染乳鼠的发病及心肌病理变化。结果 感染组乳鼠在感染CVB3m后48～72h发病，心肌病理变化以多形核细胞、单核细胞和巨噬细胞浸润为主要特征，心肌小血管壁内皮细胞受损，心肌细胞变性、肿胀；对照组乳鼠未见发病。结论 柯萨奇B3m病毒是急性心肌炎的重要病原体，其毒力及接种量与发病密切相关，本模型为研究急性病毒性心肌炎的发病机制及抗病毒药物的筛选奠定了基础。     

芪芩Ⅰ号对小鼠柯萨奇B3病毒性心肌炎的防治作用

目的:探讨复方制剂芪芩Ⅰ号(QiqinⅠ)水煎剂对柯萨奇病毒B3(CVB3)的抑制作用和对小鼠CVB3病毒性心肌炎的防治作用. 方法:①在Hep-2细胞上采用微量细胞病变抑制法,从直接灭活病毒、抑制细胞内病毒复制、阻断病毒吸附三方面研究芪芩Ⅰ号对CVB3的抑制作用. ②采用BALB/c鼠建立CVB3病毒性心肌炎的动物模型,建立病毒对照组和芪芩Ⅰ号组,然后在不同时间点处死小鼠,记录其心肌组织病变积分. 结果:①芪芩Ⅰ号水煎剂对细胞无毒且效应明显的原生药浓度是2.88 g/L和1.44 g/L. ②芪芩Ⅰ号可能具有直接灭活CVB3、抑制细胞内CVB3复制、阻断CVB3吸附细胞的作用. ③芪芩Ⅰ号组小鼠的心肌病变积分明显低于病毒对照组,二者比较有显著差异(P<0.01). 结论:体外实验证实芪芩Ⅰ号可能对CVB3有抑制作用,动物实验进一步证明芪芩Ⅰ号在体内对小鼠CVB3病毒性心肌炎有良好的防治作用.     

制备小鼠病毒性心肌炎模型最适柯萨奇病毒B3浓度的实验研究

目的寻找制备病毒性心肌炎模型的最适病毒浓度,为筛选治疗病毒性心肌炎药物提供实验模型。方法采用柯萨奇病毒B(3CVB3)Nancy株,经腹腔注射,感染BALB/C小鼠。按注射病毒浓度的不同将75只小鼠分为4组:A组20只,注射高浓度CVB(3104TCID50);B组20只,注射中等浓度CVB(3102TCID50);C组20只,注射低浓度CVB(3100TCID50);D组15只,作为正常对照组。接种后第7d随机从各组取5只小鼠,眼眶取血后处死,称重,并留取心脏标本,将剩余小鼠喂养至第21d,然后将存活小鼠全部处死。观察4组小鼠的发病特征、死亡率、心脏组织病理学变化、心脏重量/身体重量(HW/BW)比值以及血清肌酸激酶同工酶(CK-Mb)水平。结果A组小鼠症状明显较其他3组严重,死亡率达100.0%,高于其他3组,B组死亡率显著高于C组;第7d,A组HW/BW比值、心肌病理评分以及CK-Mb水平均明显高于其他3组,B组HW/BW比值、心肌病理评分以及CK-Mb水平均显著高于C组。结论小鼠的死亡率、心肌病理评分以及CK-Mb水平与接种病毒浓度密切相关,本实验制备病毒性心肌炎小鼠模型最适病毒浓度为102TCID50。     

肉桂油治疗小鼠CVB3m病毒性心肌炎的实验研究

目的:研究肉桂油(OC)对柯萨奇病毒B3m(CVB3m)诱发性小鼠病毒性心肌炎(VMC)的治疗作用.方法:0.1 mL CVB3m ip建立BALB/c小鼠VMC模型.正常对照组同法接种0.1 mL不含病毒的Eagle液,与感染病毒小鼠隔离饲养.于接种病毒72 h后给药,OC治疗组(49.1,36.7,26.5 mg/kg肉桂油,ig)、阳性药物组(50 mg/kg黄芪注射液,ip)、模型组与正常对照组(2500 mg/kg生理盐水,ig),连续给药1 wk.观察指标:累计死亡率与中位生存时间;接种病毒后10 d心肌组织光、电镜组织病理学检查;心肌匀浆MDA含量、SOD活性;血清中乳酸脱氢酶(LDH)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)含量;21 d心肌组织光镜病理检查.结果:OC 49.1和36.7 mg/kg治疗组可降低小鼠死亡率,延长中位生存时间,降低急性期血清中CK,CK-MB含量以及心肌中MDA含量,提高SOD活性;减轻急性期、亚急性期小鼠心肌组织的坏死与钙化,与模型组比较差异显著(P<0.05).结论:OC具有治疗柯萨奇病毒B3m诱发性小鼠VMC的作用.     

柯萨奇病毒B3致病毒性心肌炎动物模型的建立

病毒性心肌炎的治疗一直是临床工作者非常关注的问题[1].建立一个稳定而可靠的病毒性心肌炎动物模型,对治疗心肌炎的药物筛选及药效研究是必不可少的,心肌炎动物模型可以提供明确的病原,进行全面的心肌病理检查,适用于临床与基础研究.我们在观察各种药物治疗柯萨奇病毒(CVB3)模型鼠的作用中(另文报告),首先进行了CVB3的致病模型研究,现报告如下.     

心肌康对慢性病毒性心肌炎小鼠心肌细胞的保护作用

目的 观察心肌康对病毒性心肌炎小鼠心肌细胞的保护作用.方法 对清洁级Balb/c小鼠采用柯萨奇病毒(CVB3)腹腔注射染毒,制成慢性病毒性心肌炎动物模型,按照随机数字表法分为三组:A组为病毒性心肌炎(VMC)组、B组为心肌康组、C组氯沙坦组.另设20只腹腔接种不含病毒的Eagle's液小鼠为正常对照组,观察心肌康对模型鼠的生存率的影响及对CVB3 RNA表达、Ⅰ、Ⅲ型胶原含量的影响.结果 心肌康组、氯沙坦组小鼠的生存率明显高于病毒对照组,心肌康对CVB3感染鼠有保护作用,心肌康组对感染鼠的治疗作用要优于氯沙坦组.结论 心肌康可通过下调CVB3 RNA表达、抑制胶原增生而对心肌细胞产生保护作用.     

大蒜多糖对病毒性心肌炎一氧化氮及心肌酶的作用研究

目的探讨大蒜多糖对实验性病毒性心肌炎小鼠一氧化氮及心肌酶的影响。方法采用BALB／C小鼠腹腔注射柯萨奇病毒B3(CVB3)建立实验性小鼠病毒性心肌炎模型。小鼠随机分为正常对照组、模型组、大蒜多糖I组、大蒜多糖Ⅱ组、大蒜多糖Ⅲ组和黄芪组。注射病毒1h后给药，连续7d，于第8天处死存活鼠取材。观察小鼠存活率及心肌病理变化，测定血清心肌酶、一氧化氮(NO)含量及谷胱甘肽过氧化物酶(GSH-Px)活性。结果大蒜多糖治疗组与模型组相比小鼠存活率明显增高，心肌组织病理损伤减轻，血清心肌酶、一氧化氮含量明显降低，GSH-Px活性显著提高。结论大蒜多糖可提高病毒性心肌炎小鼠存活率、减少氧自由基和NO的产生，有利于防治实验性小鼠病毒性心肌炎。     

柯萨基B组病毒性心肌炎患儿血清TNF—α,IL—8,IL—6和sIL—2R变化

观察柯萨基Ｂ组病毒性心肌炎患儿血清肿瘤坏死因子α，白细胞介素６，白细胞介素８和可溶性白细胞介素２受体的水平变化，评价ＣｏｘＢ感染时机细胞因子的应答及其在心肌细胞免疫病理损伤中的意义。方法：检测血清采自２５例病毒性心肌炎患儿，其中１６例血清ＣｏｘＢ抗原和特异性ＩｇＭ抗体检测均阳性；另９例为血清ＣｏｘＢ抗原阴性，特异性ＩｇＢ阳性。     

Coxsackie viral myocarditis

Coxsackie viral myocarditis is a common disease, yet idiopathic dilated cardiomyopathy is a less common consequence. Insights gained from studying the Coxsackie virus B-3 murine model of myocarditis has led to the hypothesis that an acute Coxsackie viral myocarditis can result in persistent, non-viral mediated cellular responses that result in a chronic inflammatory state leading to progressive myocyte loss and ultimate development of dilated cardiomyopathy. Although the evidence linking myocarditis to dilated cardiomyopathy is circumstantial in man, the identification of defects in immunoregulation may provide the impetus to further research into the pathogenesis and ultimately the development of more rational therapies directed at modulating immune responses to alter the natural history of clinical dilated cardiomyopathy.     

Oxidative Stress in Patients With Acute Coxsackie Virus Myocarditis

To study the state of oxidative stress in patients with acute coxsackie virus myocarditis (ACM), and to investigate the pathological chain reactions of a series of free radicals and oxidative and lipoperoxidative damages in their bodies. Methods Eighty ACM patients and 80 healthy adult volunteers (HAV) were enrolled in a case-control study, in which concentrations of nitric oxide (NO) in plasma, lipoperoxides (LPO) in plasma and LPO in erythrocytes (RBC), vitamin C (VC), vitamin E (VE) and β-carotene (β-CAR) in plasma as well as activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in RBC were determined by using spectrophotometric assays. Results Compared with the average values (AV) of the above biochemical parameters (BP) in the HAV group, the AV of NO in plasma, and LPO in plasma and RBC in the ACM group were significantly increased (P=0.0001), while the AV of VC, VE, β-CAR, SOD, CAT and GSH-Px in the ACM group were significantly decreased (P=0.0001). The values of the above BP were used to estimate the relative risk ratio (RR) between the ACM group and the HAY group; the RR and its 95 % confidence interval were 12.467 (5.745～27.051), 4.333(2.126～8.834), 6.517 (3.225～13.618), 3.310 (1.598～6.858), 31.000 (12.611～76.201),4.663 (2.228～9.759), 11.769 (5.440～25.462), 3.043 (1.486～6.229) and 6.594 (3.045～14.281)respectively, and their P levels ranged from 0.002 to 0.0001. The results were asfollows: D = 22.143 - 0.017SOD + 0.008NO + 0.244LPO in RBC, Eigenvalue = 13.659,Canonical correlation = 0.965, Wilks' λ = 0.068, χ2 = 420.212, P = 0.0001. The correct rate of discrimination to the ACM group and to the HAV group was 87.5% and 95.0 %, respectively,and 91.3 % of originally grouped cases was correctly classified. Conclusion The findings in this study suggested that the oxidative stress in bodies of ACM patients was severely aggravated, and marked high oxidative constituents and low antioxidants and antioxidases in the human body might increase the relative risk of inducing acute coxsackie virus myocarditis, and measuring the values of NO in plasma, SOD and LPO in RBC might increase the correct rates of discriminatory analysis of the ACM.     

长春地区病毒性心肌炎与柯萨奇B组病毒关系的研究

本文报道长春地区20例散发性病毒心肌炎患者血中分离到柯萨奇病毒4株结合患儿双份血清对自身病毒的中和抗体的变动,可以确定分离到的病毒与心肌炎患者的相关性。同时检测20例双份血中的恢复期抗体效价4倍增高者有13例(65％)。52份心肌炎患者单份血清抗体效价达1:32以上者有32份(61.5％)。其中均以CoxB5、3、4为多见。两型抗体同时增高者约1/3以上。健康人血清60份中CoxB组病毒抗体阳性者有24份(40％)。两型抗体同时存在者11例。     

综合疗法治疗病毒性心肌炎的疗效观察

目的探讨综合疗法治疗病毒性心肌炎的疗效。方法将120例病毒性心肌炎患者随机分为治疗组及对照组，每组各60例。对照组采用常规治疗，治疗组在对照组基础上加用黄芪和大剂量维生素C。结果两组心肌酶和心功能指标均较治疗前有显著改善，治疗组改善情况优于对照组（P〈O．05），治疗组的总有效率为93．3％，高于对照组的80．O％（P〈0．05），治疗组恢复时间少于对照组（P〈O．05）。两组不良反应比较差异无统计学意义（P〉O．05）。结论黄芪联合大剂量维生素C治疗病毒性心肌炎疗效好，毒副作用少，值得临床推广应用。     

Late prognosis of viral myocarditis

85 cases of virologically proved viral myocarditis were followed up for 96.45 +/- 23.7 months for a better understanding of the late prognosis of this disease. Among these cases, 63 (74.1%) were cured, 14 (16.5%) remained with sequelae, 8 (3.5%) became chronic and 5 (5.9%) of the patients died. Most of the abnormal findings, i.e. physical signs, x-ray, ECG and UCG changes, originally existing on admission of the survived patients disappeared. The clinical features of the chronic cases resemble those of cardiomyopathy. The main causes of death were heart failure and sudden death. In order to reduce mortality, sequelae and chronicity, the importance of early virological examination, early clinical diagnosis and early and persistent treatment are stressed.     

Therapeutic effect of yupingfeng san and shengmai yin on Coxsackie B viral myocarditis

A "LDH release method" was used to determine NK cell activity in 30 cases of Coxsackie B viral myocarditis and contrasted with 20 normal volunteers. About 80% cases revealed NK cell activity deficiency. Among them, the NK activity of 24 cases (80%) was less than 14%; and 15 cases (50%) less than 10%. After Yupingfeng San and Shengmai Yin treatment for 2-3 months, their NK cell activity was elevated from 12.26 +/- 1.31% to 31.99 +/- 4.23% (P less than 0.001). At the same time, their clinical manifestations and EKG changes were improved or returned to normal.     

Clinical Observation on Shuanghuanglian powder in treating viral myocarditis of childrenin treating viral myocarditis of children

Objective: To study immune function of children viral myocarditis and to evaluate the clinical effect of Shuanghuanglian Powder (SHLP) by injection.Methods: The 62 patients of viral myocarditis were divided into two groups randomly, the SHLP group (n = 32) treated with conventional therapy plus SHLP and the conventional treatment group (n = 30) with conventional therapy alone. Their serum antibody of Coxsackie virus group B (COXB-IgM), T-lymphocyte subsets including CD₃ ⁺, CD₄ ⁺, CD₈ ⁺ and CD₄ ⁺/CD₈ ⁺ were determined with ELISA and indirect immunofluorescent assay.Results: COXB-IgM was positive in 39 of the 62 patients, which was significantly different with those of normal controls (P< 0.001). Patients’ serum level of CD₄ ⁺ cells and CD₄ ⁺/CD₈ ⁺ ratio decreased while CD₈ ⁺ increased. After treatment, the recovery of symptoms, signs and immune function in patients of the SHLP group were significantly better than those in patients treated with conventional treatment alone (P<0.01).Conclusion: Immunoregulatory disturbance is involved in children with viral myocarditis and SHLP is an effective drug in the treatment of children viral myocarditis.     

The morphological progression of viral myocarditis

In an attempt to document the morphological progression from acute idiopathic myocarditis to end-stage dilated cardiomyopathy we studied 20 patients with a diagnosis of myocarditis who had had serial endomyocardial biopsies performed with intervals of 1 month to 2 years and whose ages varied from 6 months to 62 years. Fifteen of these patients were treated with immunosuppressive drugs for myocarditis. Ten out of 15 treated patients stabilized clinically. In the remaining 5 cases there was worsening congestive heart failure and 1 patient underwent cardiac transplantation. Of the 5 patients who did not receive immunosuppression, 2 stabilized spontaneously, and 3 developed heart failure, 2 of whom subsequently had cardiac transplants. Whether the patients received immunosuppression or not, in all cases, the inflammatory infiltrate was less but the myocardium developed significant hypertrophy with an increase in interstitial fibrosis and in 8 cases the morphological changes were those of dilated cardiomyopathy. From the morphological standpoint of this study we have shown some evidence that dilated cardiomyopathy can be the end result of acute myocarditis. It appears that not every case of acute myocarditis progresses to dilated cardiomyopathy and that steroid treatment does not necessarily prevent progression of myocarditis to dilated cardiomyopathy.