B族维生素在酒精性心肌病发病中的作用

Role of B vitamins in alcoholic cardiomyopathy

目的探讨B族维生素在酒精性心肌病(alcoholic cardiomyopathy,ACM)发病中的作用。方法 106只Wistar大鼠随机分为乙醇组41只,观察组37只和对照组28只。乙醇组和观察组随意饮用体积分数10%乙醇及体积分数60%乙醇灌胃制备ACM模型,观察组同时给予维生素B612mg/(kg·d)、维生素B120.09mg/(kg·d)、叶酸4mg/(kg·d),对照组饮用水及等量生理盐水灌胃,3组均喂养24周。分别于入组及喂养8、16、24周时行超声检查,测定左心室舒张末期内径(left ventricular end-diastolic dimension,LVEDd)、左室射血分数(left ventricular ejection fraction,LVEF)、左心室短轴缩短率(fractional shortening,FS),采用化学发光法测定血浆同型半胱氨酸(homocysteine,Hcy)水平,并计算心肌组织基质金属蛋白酶(matrix metalloprotein-9,MMP-9)及胶原纤维含量。结果喂养24周时乙醇组大鼠左心腔扩大,室壁厚度变薄,超声心动图符合ACM改变,提示造模成功;喂养16、24周时,乙醇组LVEDd[(6.87±0.55)、(7.54±0.49)mm]、观察组LVEDd[(5.70±0.60)、(7.13±0.41)mm]较对照组宽[(4.75±0.39)、(4.72±0.32)mm](P<0.05),乙醇组LVEF[(51.81±8.16)%、(43.24±5.41)%]、观察组LVEF[(62.79±7.91)%、(48.50±5.86)%]低于对照组[(78.07±3.77)%、(76.93±4.73)%],乙醇组FS[(30.51±2.72)%、(21.94±2.94)%]、观察组FS[(37.29±4.12)%、(24.57±3.14)%]低于对照组[(46.81±2.39)%、(44.95±3.38)%](P<0.05);喂养16周时乙醇组LVEDd较观察组宽(P<0.05),LVEF、FS低于观察组(P<0.05);喂养8、16、24周时观察组血浆Hcy水平[(4.54±1.53)、(4.93±1.63)、(5.16±2.03)μmol/L]低于对照组[(9.99±2.59)、(10.00±3.10)、(10.41±2.40)μmol/L]和乙醇组[(18.12±3.08)、(26.31±4.03)、(30.87±3.63)μmol/L](P<0.05),对照组低于乙醇组(P<0.05);喂养16、24周时,乙醇组[(0.160 9±0.019 0)%、(0.262 5±0.013 6)%]、观察组[(0.116 4±0.021 6)%、(0.245 5±0.025 4)%]MMP-9表达水平高于对照组[(0.054 5±0.006 8)%、(0.055 9±0.008 3)%](P<0.05),且喂养16周时观察组MMP-9表达低于乙醇组(P<0.05);喂养16、24周时乙醇组胶原纤维表达[(0.102 3±0.012 0)%、(0.224 1±0.025 7)%]、观察组胶原纤维表达[(0.074 5±0.009 2)%、(0.202 0±0.044 5)%]高于对照组[(0.005 2±0.000 9)%、(0.005 5±0.000 9)%](P<0.05),且喂养16周时观察组胶原纤维表达低于乙醇组(P<0.05)。结论补充B族维生素可能通过降低血浆Hcy水平来而延缓ACM发病。

Objective To explore the role of B vitamins in delaying the onset of alcoholic cardiomyopathy （ACM）. Methods A total of 106 male Wistar rats were randomly divided into ethanol group （n=41）, observation group （n=37） and control group （n= 28）. Ethanol group and observation group were treated by drinking 10% ethanol and gavage by 60% ethanol to establish ACM models. Observation group received oral administration of vitamin B6 （12 mg/（kg · d））, vitamin B12 （0.09 mg/（kg · d）） and folic acid （4 mg/（kg · d））. Control group received gavage by water. All three groups were fed for 24 weeks and underwent ultrasound at the time points of before treatment, and in 8, 16 and 24 weeks after treatment to measure left ventricular end-diastolic dimension （LVEDd）, left ventricular ejection fraction （LVEF） and fractional shortening （FS）. Homocysteine （Hcy） level was detected, and the concentrations of matrix metalloprotein-9 （MMP-9） and collagen fiber of myocardium were calculated. Results After 24-week feeding, the left ventricular cavity was enlarged and the ventricular wall became thinner, and the echocardiography was in accordance with the change of ACM, indicating the success of model establishment in ethanol group. In 16 and 24 weeks, LVEDd values were significantly larger in ethanol group （（6.87±0.55）, （7.54±0.49） mm） and observation group （（5.70±0.60）, （7.13± 0.41） mm） than those in control group （（4.75±0.39）, （4.72±0.32） mm） （P〈0.05）, LVEF values were significantly smaller in ethanol group （（51.81±8.16）M, （43.24±5.41）%） and observation group （（62.79±7.91）%, （48.50± 5.86） %） than those in control group （（78. 07±3. 77）%, （76. 93±4. 73）%） （P〈0.05）, and FS values were significantly smaller in ethanol group （（30.51±2.72） %, （21.94±2.94）%） and observation group （（37.29±4.12） %, （24.57±3.14）%） than those in control group （（46.81±2.39）%, （44. 95±3.38）%） （P〈0.05）. LVEDd value was significantly larger in ethanol group than that in observation group in 16 weeks （P〈0.05）, and LVEF and FS values were significantly smaller in ethanol group than those in observation group （P〈0.05）. In 8, 16 and 24 weeks, the plasma Hcy levels （（4.54±1.53）, （4.93±1.63）, （5.16±2.03）μmol/L） in observation group were significantly lower than those in control group （ （9.99 ± 2.59）, （10.00 ± 3.10）, （10.41 ± 2.40） p.moI/L） and ethanol group （（ 18.12 ± 3.08）, （26.31±4.03）, （30.87±3. 63） μmol/L） （P〈0.05）, and were lower in control group than those in ethanol group （P〈0.05）. In 16 and 24 weeks, the MMP-9 levels were significantly higher in ethanol group （（0. 160 9±0. 019 0）%, （0. 262 5±0. 013 6）%） and observation group （（0. 116 4±0. 021 6）%, （0. 245 5±0. 025 4）%） than those in control group （（0. 054 5± 0. 006 8）%, （0. 055 9±0. 008 3）%） （P〈0.05）, and MMP-9 level was significantly lower in observation group than that in ethanol group in 16 weeks （P〈0.05）. In 16 and 24 weeks, the amounts of myocardial collagen fiber were significantly higher in ethanol group （（0. 102 3±0. 012 0） %, （0. 224 1±0. 025 7）%） and observation group （（0. 074 5±0. 009 2） %, （0. 202 0±0. 044 5） %） than those in control group （（0. 005 2±0. 000 9） %, （0. 005 5± 0. 000 9）%） （P〈0.05）, and was significantly lower in observation than that in ethanol group in 16 weeks （P〈0.05）. Conclusion Compensation of B vitamins could delay the onset of ACM by lowering the plasma Hcy level.