CD28单克隆抗体对病毒性心肌炎小鼠的治疗作用

Therapeutic role of the CD28 monoclonal antibody in mice with viral myocarditis

目的探讨CD28单克隆抗体(CD28 mAb)对柯萨奇病毒B3(CVB3)病毒性心肌炎(VMC)小鼠的死亡率、心肌病理改变及病毒滴度的影响。方法随机将106只BALB/c小鼠分为CD28 mAb组16只、病毒组40只I、gG组40只及正常对照组10只,腹腔注射半数组织感染量(TCID50)为10-6/mL的柯萨奇B3病毒0.15 mL,正常对照组接种0.15 mL的Eagle氏液。CD28 mAb组I、gG组接种病毒后67、2 h分别接种CD28 mAb(0.1 mg/kg)和IgG(0.1 mg/kg)。于接种病毒后第7天处死所有小鼠,取心脏,在光镜下观察心肌病理变化,采用实时荧光定量PCR(RQ-PCR)检测心肌组织中CVB3mRNA的表达。结果CD28单克隆抗体组小鼠死亡率、心肌病理积分、心肌CVB3mRNA均低于病毒对照组(P均<0.05)。结论CD28单克隆抗体可降低心肌病毒滴度,减轻VMC小鼠心肌炎症,降低VMC小鼠死亡率。

Objective To investigate the effect of the CD28 monoclonal antibody （CD28 mAb） on mortality, viral titers of myocardium and pathologic changes of myocardium in CVB3 myocarditis in mice. Methods A total of 106 BALB/c male mice were used in the experiments, which were randomly divided into the CD28 mAb group （ 16 mice）, the CVB3 group （40 mice）, the IgG group （40 mice） and the control group （ 10 mice）. Mice in the former three groups were intraperitoneally inoculated with 0. 15 mL CVB3 （TCIDS0 10-6/mL） and in the control group with 0.15 mL eagle, and then mice in the IgG and the CD28 mAb groups were inoculated with IgG（0.1 mg/kg） and CD28 mAb（0. 1 mg/kg） at 6 hours and 72 hours post-inoculation（p.i. ）. The surplus mice in each group were sacrificed on day 7. The heart was taken and pathologic changes of cardiac muscle cells were observed under light microscopy, and expression of CVB3 mRNA of myocardium was determined by the real-time quantitative poly- merase chain reaction（RQ-PCR） method. Results The mice mortality rate in the CD28 mAb group was lower than that in the CVB3 group （80% vs 50%, P 〈 0.05） ; the pathological score（8.88 ± 2.95 vs 5.25 ± 1.91, P 〈 0.05） and the CVB3mRNA expression level（3.48 ± 2.89 vs 0.51 ± 1.80, P 〈 0.05）. Conclusion CD28 mAb could decrease the expression of CVB3 mRNA, relieve myocardium inflammation and reduce the mortality rate.