【作者】 寿折星；

【导师】 沈霖；

【作者基本信息】 华中科技大学 ， 中西医结合临床， 2010， 博士

【摘要】 目的复制椎动脉型颈椎病兔动物模型,探讨复方川脊方治疗兔椎动脉型颈椎病动物模型效果；探讨兔椎动脉型颈椎病动物模型椎动脉基质金属蛋白酶-2(matrix metalloproteinase-2, MMP-2)、肌浆球蛋白(α-smooth muscle actin,α-SMA)表达的意义及复方川脊方的干预效果；完善椎动脉型颈椎病关于血管病变的发病机制,发展中药治疗椎动脉型颈椎病的作用机理。方法40只日本大耳兔随机分为四组：空白组,模型组,颈复康组,川脊方组。用硬化剂注射法造模,10 ml消痔灵注射于日本大耳兔右侧颈3至颈5椎体横突处,并于第二周,第四周各重复一次。四周后,经颅多普勒(TCD)检测显示模型组,颈复康组,川脊方组日本大耳兔右侧血流速度较左侧显著降低,搏动指数和阻力指数较右侧均显著提高(p<0.05),脑干听觉诱发电位显示模型组,颈复康组，川脊方组日本大耳兔右耳Ⅲ,Ⅴ波潜伏期均较注射前显著延长,差异有统计学意义(p<0.05)。显示造模成功。药物干预四周：模型组给予20 ML生理盐水灌胃,颈复康组给予20 ML颈复康混悬液灌胃,川脊方组给予20ML川脊方混悬液灌胃,均为每日一次。治疗四周后TCD检测血流速度,搏动指数和阻力指数,脑干听觉诱发电位检测双耳Ⅰ、Ⅲ、Ⅴ波潜伏期,血流变仪检测全血粘度及血浆粘度,常规HE染色测量血管壁中膜厚度,免疫组织化学检测血管α-SMA变化及MMP-2的表达。结果与空白组相比模型组血流速度降低,搏动指数和阻力指数均显著提高,Ⅲ,Ⅴ波潜伏期均显著延长,全血粘度及血浆粘度增加,管壁增厚,α-SMA和MMP-2表达增多,差异有统计学意义(p<0.05)；与模型组及颈复康组相比,川脊方组血流速度升高,搏动指数和阻力指数均降低,全血粘度及血浆粘度降低,管壁增厚受抑制,α-SMA表达减少,MMP-2表达较少,差异有统计学意义(p<0.05)。川脊方组与模型组相比,Ⅲ，Ⅴ波潜伏期缩短,差异有统计学意义(p<0.05)。复方川脊方组与颈复康组相比Ⅲ，Ⅴ波潜伏期无明显差异(p>0.05)。四组中Ⅰ波潜伏期均无明显改变(p>0.05)。结论复方川脊方能有效治疗兔动物模型椎动脉型颈椎病,提高平均血流速度,降低搏动指数和阻力指数,改善脑干供血,降低全血粘度及血浆粘度；血管壁增殖与重构是椎动脉型颈椎病血供减少的机制之一,复方川脊方能有效抑制椎动脉血管增殖与重构。更多还原

【Abstract】 ObjectiveFirst of all:to rebuild the rabbits model of vertebral artery type of cervical spondylosis and explore the efficacy compound chuanji formula in treatment of rabbits model of cervical spondylosis. The second:to detect the expression of MMP-2 andα-SMA in the vertebral artery and the interference effects of compound chuanji formula to it. The third:to interpret the pathogenesis of the vertebral artery in vertebral artery type cervical spondylosis and develop the mechanism of Chinese medicine in treatment of vertebral artery type of cervical disease.MethodsForty rabbits were randomly divided into four groups:the normal group, the control group, the Jingfukang group (JFKG) and the chuanji formula group (CJFG). The method of injecting sclerosing agent was used to induce the vertebral artery type of cervical spondylosis animal model.10 mL scleroing agent was injected into the left side of C3 to C5 cervical vertebra next to the edge of transverse process with the syringe needle. The above steps were repeated at the 1st day of the 2nd and 4th week, respectively. Four weeks later, the TCD detection showed that the pulsatility index, resistent index were significantly higher and the blood flow rate was remarkedly slower in the left side vertebral artery than those in the right side vertebral artery in the control group, JFKG and CJFG respectively (p<0.05); Brainstem auditory evoked potentials (BAEP) showed thatⅢ,Ⅴlatencies were longer than four weeks ago in the control group, JFKG and CJFG (p<0.05). It showed the animals model were successfully reproduced.The control group, JFKG and CJFG were treated with 20 ML Normal saline,20 ML suspended compound chuanji formula or 20 ML suspended Jingfukang granule respectivily with intragastric administration, once a day. After four weeks therapy, the transcranial doppler was used to detect the blood flow rate、pulsatility index and the resistent index of the vertebral artery;BAEP apparatus detected theⅠ、Ⅲ、Ⅴlatency; the blood flow rheometer was. used to detected the plasma viscosity and the blood viscosity; the HE staining was used to measure the thickness of tunica media vasorum, the immunohistochemistry was used to detect the expression ofα-SMA and the expression of MMP-2 in the vertebral artery.ResultsThe plasma viscosity, blood viscosity, pulsatility index, resistent index, thickness of tunica media vasorum, expression ofα-SMA and the expression of MMP-2 were significantly higher in the model group than those in the normal group, theⅢ,Ⅴlatency was significantly longer (p＜0.05), in the contrast, the blood flow rate was remarkably decreased (p＜0.05). The plasma viscosity, blood viscosity, pulsatility index, resistent index, thickness of tunica media vasorum, expression ofα-SMA and the expression of MMP-2 were decreased significantly in the CJFG compared with the normal group and the control group (p<0.05), and the blood flow rate was increased remarkably (p<0.05) Compared with the control group, theⅢ,Ⅴlatency was significantly longer in the CJFG (p＜0.05); Compared with the JFKG, theⅢ,Ⅴlatency was the samilar (p>0.05).TheⅠlatency was not changed too much in the four group (p＞0.05)ConclusionCompound chuanji formula is effective in treatment of the animal model of vertebral artery type cervical spondylosis; The tunica media vasorum proliferation is one of the mechanism of blood-supply insufficient in vertebral artery type of cervical spondylosis; It would improve the blood supply to the brain stem, decrease the plasma viscosity, blood viscosity, pulsatility index and resistent index, also increase the blood flow rate. Proliferation and reconstitution of vertebral artery is one of the mechanism of vertebral artery type of cervical spondylosis; CJP is effective in inhibit the proliferation and reconstitution of vertebral artery.更多还原