摘要
目的：探讨颈痛宁丸对椎动脉型颈椎病治疗作用及相关机制。
方法：取健康新西兰大耳白家兔70只,雌雄各半,体重2.5-3.0kg,各家兔编号。采用TCD检测各家兔脑血流,记录各家兔椎-基底动脉血流速度。采用单侧颈椎C3-C5横突侧面注射硬化剂法制备椎动脉型颈椎病家兔模型。再次经TCD检测椎-基底动脉血流速度,确定模型制备成功。挑选40只成功模型家兔,随机分为5组,每组8只。阳性对照组给予颈复康颗粒1.0g/kg、颈痛宁丸高、中、低剂量组分别给予颈痛宁丸2.0g/kg、1.0g/kg、0.5g/kg,模型组给予等容积生理盐水,另取8只未造模家兔作为空白对照组,动物正常饲养。各组动物每日给药一次,连续4周,于给药第27天进行TCD检测,第28天药后30min采血、取颈部注射部位肌肉组织和脑组织。以化学法检测家兔血清NO浓度；酶联免疫法检测血浆ET含量、IL-1β含量、TNF-a含量；在光镜下观察颈部注射部位肌肉和脑组织形态、细胞结构、结缔组织、炎性因子、瘀血等情况。另取小白鼠50只,随机分为5组,空白对照组正常饲养,阳性对照组给予阿司匹林0.3 g/kg,颈痛宁丸高、中、低剂量组分别给予颈痛宁丸5.4g/kg.2.7g/kg.1.35g/kg.各组动物每日给药一次,连续7天。末次药后30min,通过乙酸刺激扭体反应观察颈痛宁丸的镇痛作用。
结果：1.颈痛宁丸对椎动脉型颈椎病模型家兔治疗作用的研究:TCD检测结果表明,给药后颈痛宁丸高、中、低剂量组左椎动脉Vm、右椎动脉Vm、基底动脉Vm与给药前相应速度比有显著增加。其中高剂量组给药后左椎动脉Vm、右椎动脉Vm、基底动脉Vm与给药前相应速度比有显著差异(P<0.01、P<0.01、P<0.05),中剂量组给药后左椎动脉Vm、右椎动脉Vm与给药前相应速度比有显著差异(P<0.05)。用药后,各给药组与模型对照组比,左侧椎动脉Vm、右侧椎动脉Vm、基底动脉Vm均有不同程度的提高。其中高剂量组左侧椎动脉Vm、右侧椎动脉Vm、基底动脉Vm与模型对照组比有明显差异(P<0.01、P<0.05、P<0.01),中剂量组左侧椎动脉Vm与模型对照组比有明显差异(P<0.05)。血液检测结果显示,颈痛宁丸高、中剂量组血浆中ET含量与模型对照组比较有显著减少(P<0.01、P<0.05)；颈痛宁丸高、中剂量组血浆IL-1β含量与模型对照组比较显著减少(P<0.05)；颈痛宁丸高、中剂量组血浆TNF.α含量与模型对照组比明显降低(P<0.01、P<0.05)；颈痛宁丸高、中剂量组血清NO含量与模型对照组比明显升高(P<0.01、P<0.05)。光镜下观察得出,各给药组颈部注射部位肌肉组织和脑组织细胞结构变化和结缔组织增生、炎性细胞数量、瘀血等现象较模型对照组比有明显改善。2.颈痛宁丸抗痛作用的实验研究：各给药组动物扭体次数较空白组比明显减少,其中颈痛宁丸高、中剂量组扭体次数与模型对照组比有显著差异(P<0.05)。
结论：颈痛宁丸对椎动脉型颈椎病家兔有一定的治疗作用,其作用机制可能与改善血液循环,调节血管舒缩,抑制炎性因子,增强机体抗痛能力有关。
Objective:To explore the effects and mechinisms of Jingtongning-pill (JTNP), which has effects on cervical spondylotic vertebral arteriopathy(CSA).
Methods:70 healthy New Zealander rabbits in half respectively male and female,weighing 2.5kg to 3.Okg,were numbered.All rabbits were measured the mean velocity (Vm) in vertebral arteries(VA) and basilar arteries(BA) using transcranial doppler(TCD).Then all rabbits were injected tissue sclerosing liquid into the soft tissue on the left side of cervical vertebral transverse protuberance to set up the CSA models.Measured the Vm in left VA,right VA and BA using TCD once more to confirm the successful models.Next,Selected 40 successful model rabbits and grouped them into 5 groups randomly,8 in each group.All groups were administered of relevant drugs for 4 weeks,once a day.The positive group was administered Jingfukang-granule1.0g/kg.JTNP was administrated to the high-dose group 2g/kg,the middle-dose group 1g/kg,the low-dose group 0.5g/kg,respectively. The model control group was given same amount of saline. The normal group was composed of another 8 healthy rabbits and was fed on normal diet.27days after first administration,all rabbits were measured the mean velocities in left VA,right VA and BA using TCD.Next day,tested the content of ET,IL-1β,TNF-αin plasma,NO in serum,and observed the histopathological change of the injection tissue and brain by light microscope about histomorphology,cytoarchitecture,hyperplasia of connective tissue, increaseing of inflammatory cells,blood stagnation and so on.Besides,50 mouses were randomly signed into 5 groups,10 each group.The positive control group was administered of aspirin0.3g/kg.JTNP was administered to the high-dose group 5.4g/kg,the middle-dose group 2.7g/kg,the low-dose group 1.35g/kg,respectively.The normal control group was given same amount of saline,all groups were administered for a week.Half an hour after the last administration,all groups were injected acetic acid into belly and then observed the amount of body twisting in 15 minutes.
Results:1.The detecting results by TCD show that after administration the mean velocities in left VA, right VA and BA were faster than the mean veloci-ties before administration.The mean velocities in left VA, right VA and BA of the high-dose group were very different from the mean velocities in left VA, right VA and BA of the model control group(P<0.01,P<0.01,P＜0.05,P<0.01).The mean velocities in left VA and right VA of the middle-dose group were also different from the mean velocities before administration(P<0.05).After administration, the mean velocities in left VA, right VA and BA were faster than the mean velocities in left VA and right VA of the model control group,the mean velocities in left VA, right VA and BA of the high-dose group were very different from the mean velocities in left VA and right VA of the model control group(P<0.01,P<0.05,P<0.01).The Vm in left VA of the middle-dose group was also different from the Vm in left VA of the model control group(P<0.05).In the high-dose group and the middle-dose group,the content of NO in serum was obvious higher than the model control group(P<0.01,P<0.05).In the high-dose group and the middle-dose group,the ET content in plasma was obvious lower than the model control group(?<0.01,P<0.05).In the high-dose group and the middle-dose group,the content of IL-lβin plasma was obvious lower than the model control group (P<0.05). In the high-dose group and the middle-dose group,the content of TNF-a in plasma was obvious lower than the model control group(P<0.01,P<0.05).By light microscope the observed results showed that the phenomenons,such as histomorphology,Cytoarchitecture, hyperplasia of connective tissue,increasing of inflammatory cells,blood stagnation and so on,of all tested groups were superior to the model control group. 2.JTNP analgesia study showed that the times of body twisting of the high-dose group and the middle-dose group were less than the model control group (P<0.05).
Conclusion:JTNP has obvious therapeutic effects on cervical spondylotic vertebral arteriopathy modal rabbits.The mechenisms may be relateimproving the blood circulation, adjusting vessels,restraining inflammatory factors, boosting body ability of resistance pains and so on.
引文
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