氧化苦参碱对慢性病毒性心肌炎小鼠心肌的保护作用

Protection of Oxymatrine on Myocardium of Mice with Chronic Viral Myocarditis

目的观察慢性病毒性心肌炎(CVMC)小鼠血清抗心肌肌球蛋白抗体(AMA)的表达和心肌胶原容积积分(CVF),以及氧化苦参碱对其的干预作用和对心肌的保护作用。方法以柯萨奇病毒B3株(CVB3)重复增量感染BALB/c小鼠,建立CVMC模型(n=60)。正常对照组(n=8)同期腹腔注射等体积9 g.L-1盐水。42 d将CVMC模型组存活小鼠随机分为CVMC对照组(n=8)、氧化苦参碱干预组(n=8)。氧化苦参碱干预组小鼠给予氧化苦参碱100 mg.kg-1.d-1灌胃,1次.d-1。CVMC对照组及正常对照组同期给予9 g.L-1盐水灌胃。干预28 d后处死各组小鼠。计算各组小鼠心脏/体质量比(HW/BW);心肌切片行胶原组织特异性染色,计算心肌组织中CVF;ELISA法检测其血清AMA的表达。结果CVMC对照组小鼠HW/BW(0.007 9±0.000 3)、CVF[(15.30±1.08)%]及血清中AMA吸光度(A)值(0.286±0.053)较正常对照组HW/BW(0.005 5±0.000 2)、CVF[(6.84±1.11)%]及AMAA值(0.160±0.050)均显著增高(Pa<0.01)。AMA阳性组HW/BW[(0.007 60±0.000 68)%]、CVF[(14.328±2.63)%]及AMAA值(0.313±0.028)较阴性组HW/BW[(0.006 30±0.000 91)]、CVF[(9.195±3.061)%]及AMAA值(0.189±0.051)均显著增高(Pa<0.01)。氧化苦参碱干预后HW/BW(0.006 8±0.000 4)、CVF[(9.94±1.35)%]及血清中AMAA值(0.229±0.054)均较CVMC对照组HW/BW(0.007 9±0.000 3)、CVF[(15.30±1.08)%]及血清中AMAA值(0.286±0.053)显著降低(Pa<0.05)。结论CVMC小鼠血清AMA和CVF表达均增高,氧化苦参碱可下调二者的表达,抑制CVMC小鼠的心肌重构。

Objective To observe the expression of anti -cardiac mynsin antibody（AMA） and the collagen volume fraction （CVF） in serum in mice with chronic viral myoearditis （CVMC） ,and to explore the preventive and protective function of oxymatrine on myoeardium. Methods BALB/e mice （n = 60） were infected with eoxsaekievirus B3 （ CVB3 ） of increased dose biweekly to establish CVMC model. Mice in normal control group （/z = 8） received equal -volume 9 g ~ L-L saline without CVB3 at the same time. The surviving mice in CVMC model group were randnmly divided into CVMC enntrol group （n = 8） and oxymatrine therapy group（n = 8） at the 42^th day. From then on, mice in oxymatrine therapy group were treated with oxymatrine at the dose of 100 mg · kg^-1·d^-1 by gastric perihsion once a day for 28 clays,and meanwhile mice in CVMC control group and the normal control group received equal - volume 9 g · L^-1 saline by gastric perfusion ever）, day. Then all mice were sacrificed at the end of the experiment. The ratio between heart weight to body weight （HW/BW） was calculated. Myocardium slides were stained with collagen specifie Pieric acid - Sirius red staining,and the CVF was calculated with image analysis software. The serum level of AMA （optical density value,A value） was detected by enzyme - linked immunosorbent assay （ELISA）. Results HW/BW （0.007 9±0. 000 3）,CVF [ （15.30 ±1.08）% ] and the A value of AMA （0. 286±0. 053 ） in mice of CVMC control group were increased significantly compared with those in normal control grnup HW/BW （0. 005 5±0. 000 2 ）, CVF [ （ 6.84 ± 1. 11 ） % ], the A value of AMA （0. 160 ±0. 050） （ P 〈0. 01 ） . While for mice of AMA positive group, HW/BW （ 0. 007 60 ± 0. 000 68 ）, CVF [（ 14. 328± 2.63 ） % ], and the A value of AMA （0.313 ±0. 028 ） were significantly higher than those of mice in AMA negative group HW/BW [ （0. 006 3 ± 0. 000 91 ） % ], CVF[（9.195±3.061）%],theA value ofAMA （0. 189±0.051）（Pa〈0. 01）.HW/BW （0.006 8±0.0004）,CVF[（9.94±1.35）%]. and the A value of AMA （0. 229 ±0. 054） in mice of oxymatrine therapy group were significantly lower compared with HW/BW （0. 007 9 ±0. 000 3 ）, CVF[ （ 15.30 ± 1.08 ） CA ] and the A value of AMA （0. 286±0. 053 ） in mice of CVMC control group（ P 〈0. 05 ）. Conclusions The expression level of AMA in serum and CVF in myoeardium were increased in CVMC mice. Oxymatrine might down - regulate the expression level of AMA and decrease CVF,so as to inhibit myocardial remodeling.