黄连素对兔颈动脉球囊损伤后内膜增生与血管重塑的影响

Effect of Berberine on Intimal Hyperplasia and Vascular Remodeling After Balloon Withdrawal Injury of Rabbit Carotid artery

目的观察黄连素对兔颈动脉球囊损伤后血中一氧化氮、内皮素1、血小板源生长因子和转化生长因子β1水平的影响以及对新生内膜增生与血管重塑的作用,并初步探讨其可能机制。方法将日本大耳白兔随机分为假手术组、模型组、黄连素组和辛伐他汀组,分别检测血一氧化氮、内皮素1、血小板源生长因子和转化生长因子β1水平,并取颈动脉切片作病理形态学观察,利用计算机图像分析系统测量血管新生内膜厚度、管腔面积、新生内膜面积、内弹力板围绕面积、中膜面积和外弹力板围绕面积,并计算新生内膜/中膜面积及内膜增生指数。结果黄连素组一氧化氮较模型组和辛伐他汀组显著升高(65±13比32±13和40±16,P<0.01);黄连素组内皮素1、血小板源生长因子和转化生长因子β1(58±11、145±12和163±33)较模型组(91±16、183±33和210±28)均显著降低(P<0.01)。黄连素组血管新生内膜厚度、新生内膜面积、新生内膜面积/中膜面积和内膜增生指数(32.91±4.20、10.22±1.91、0.31±0.06和19.51±3.48)较模型组显著减小(59.54±7.17、18.66±4.57、0.62±0.14和28.32±4.25),较假手术组显著增加(14.11±2.95、2.73±0.35、0.10±0.03和9.22±0.87)(P<0.01);黄连素组管腔面积、内弹力板围绕面积和外弹力板围绕面积(48.56±4.71、59.45±2.42和91.12±7.19)较模型组(27.33±3.47、45.82±4.65和75.75±1.05)及假手术组(35.08±8.00、37.14±3.25和68.38±3.30)均显著增加(P<0.01),但4组中膜面积差异无显著性(P>0.05)。结论黄连素可能通过调节一氧化氮、内皮素1、血小板源生长因子和转化生长因子β1的水平直接或间接抑制新生内膜增生与不良的血管重塑。

Aim Toobserve the effect of Berbefine on thelevels ofendothelium-1 （ET-1）, nitric oxide （NO） platelet derived growth factor （PDGF）, transfer growth factor-β1 （TGF-β1） and intima hyperplasla and vascular remodeling after balloon withdrawal injury of rabbit carotid artery, and to evaluate its mechanism. Methods Fourty Japanese rabbits were allocated randomly into 4 groups： artificial group（ n = 7）, model group（ n = 11 ）, berbedne group （ n = 11 ） and simvastatin group（ n = 11 ）. The balloon endothelium denud-ation were made in carotid artery of all rabbits of the later three groups in the condition of anesthesia, and they were injected respectively with 0.9% sodium chloride, berbefine and simvastatin liquid （2.5 mg/kg everyday）. After 15 days, thelevels of ET- 1, NO andPDGF, TGF-β1 ofall groups were detected; at the same time , we observed the morpholngic change of injured artery and took photos, and intimal thickness（IT）, intimal area（IA）, luminal area （LA）, internal elastic lamina （IEL）, medial area （MA） and external elastic lamina （EEl.） of all groups were measured with the system of computer photo analysis, IMMA and intima hyperplasia index （IHI） were computed. Results The concentration of NO of berberine group（65 ± 13） were increased significantly compared with model group （32 ± 13）and simvastafin group（40± 16）（P 〈 0. 01）; the levels ofET-1 and PDGF, TGF-β1 ofberbefine group（58± 11,145± 12,163± 33） were markedly decreased compared withmodelgroup（91±16,183±33,210±28） （P〈0.01）. IT, IA, IA/MA and IHI of berberine group（32.91±4.20,10.22 ± 1.91,0.31 ± 0.06,19.51 ± 3.48） were decreased significantly than model group （59.54 ± 7.17,18.66 ± 4.57, 0.62 ± 0. 14, 28.32± 4.25）but higher than artificial group（ 14.11 ± 2.95,2.73± 0.35,0.10± 0.03, 9.22± 0.87） （P 〈 0.01）; and LA, IEL, EEL of berbedne group （48.56±4.71, 59.45±2.42, 91.12±7.19）were increased deadly than model group （27. 33±3.47, 45.82±4.65, 75.75± 1.05） and artificial group（35.08± 8.00, 37.14±3.25, 68.38± 3.30）（P〈0.01）, but MA of 4 groupshave nomarketablechange（P〉0.05）. Conclusion Be± can increase the levels of NO , decrease tbe concentration of ET-1, PDGF, TGF-β1 ; and make LA, IEL, EEL enlarged but IT, IA, IA/MA, IHI reduced; which can be the possible mechanism that inhibits intima hyperplasia and vascular remodeling.