盐酸苯环壬酯对大鼠后循环缺血性眩晕和小鼠位置性眩晕的改善作用
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摘要
目的研究盐酸苯环壬酯的抗眩晕作用。方法利用双侧颈总动脉结扎法制备大鼠脑缺血模型,大鼠ig给予盐酸苯环壬酯0.1~4.0 mg·kg~(-1),每天2次,连续3 d,结合激光多普勒脑血流仪检测盐酸苯环壬酯对脑血流量变化的影响。通过XY-5双轴变速旋转刺激制备小鼠眩晕症模型,小鼠ig给予盐酸苯环壬酯1.4~5.6 mg·kg~(-1)后变速旋转刺激30 min,检测自发活动的变化;小鼠ig给予盐酸苯环壬酯1.4~8.4 mg·kg~(-1)30 min后,通过检测胃酚红排空率指标观察盐酸苯环壬酯对小鼠胃平滑肌的影响。结果大鼠双侧颈总动脉结扎24 h后脑血流量显著减少(P<0.01);与模型组比较,盐酸苯环壬酯0.5,2.0和4.0 mg·kg~(-1)可显著增加缺血大鼠脑血流量(P<0.05)。通过旋转刺激后,模型小鼠自发活动的总路程减少(P<0.05),运动速度减慢(P<0.05);与模型组比较,盐酸苯环壬酯2.8和5.6 mg·kg~(-1)可增加眩晕小鼠总路程和运动速度(P<0.05);盐酸苯环壬酯5.6和8.4 mg·kg~(-1)降低小鼠胃酚红排空率(P<0.05)。结论盐酸苯环壬酯增加脑血流量,改善后循环缺血,对眩晕的呕吐症状和运动功能具有显著的改善作用。
OBJECTIVE To evaluate the anti-vertigo effect of phencynonate hydrochloride. METHODS To detect the improvement of phencynonate hydrochloride on cerebral blood flow, a rat model was established with bilateral common carotid arteries occlusion. Phencynonate hydrochloride 0.1-4.0 mg·kg~(-1)was ig given, twice a day for three consecutive days and the alteration of cerebral blood flow was measured with laser Doppler flowmetry. Rotating acceleration equipment was used to provocate mouse vertigo for 30 min, and the spontaneous locomotor activities were tested for occurrence of vertigo in mice. Phencynonate hydrochloride 1.4-5.6 mg·kg~(-1)was ig given before rotating acceleration. Gastric phenol red emptying rate was used to determine the anti-nausea effect of the test drug in mice 30 min after phencynonate hydrochloride 1.4-8.4 mg·kg~(-1)was ig given. RESULTS The cerebral blood flow of the rat model with bilateral common carotid arteries occlusion was reduced significantly after 24 h(P<0.01). Compared with the model group, phencynonate hydrochloride(0.5, 2.0 and 4.0 mg·kg~(-1)) increased the cerebral blood flow in a dose-dependent manner in rats with cerebral ischemia(P<0.01). The spontaneous locomotor activities were significantly reduced after vertigo stimulation in mice(P<0.05).Compared with the model group, phencynonate hydrochloride(2.8 and 5.6 mg·kg~(-1)) increased the movement distance and speed of vertigo mice(P<0.05). Phencynonate hydrochloride(2.8, 5.6 and8.4 mg·kg~(-1)) inhibited the gastric emptying of mice(P<0.05). CONCLUSION Phecynonate hydrochloride can improve the cerebral blood flow and locomotor activities in vertigo rats, while inhibiting gastric emptying, which points to the therapeutic potential of phencynonate hydrochloride for vertigo in clinic.
OBJECTIVE To evaluate the anti-vertigo effect of phencynonate hydrochloride. METHODS To detect the improvement of phencynonate hydrochloride on cerebral blood flow, a rat model was established with bilateral common carotid arteries occlusion. Phencynonate hydrochloride 0.1-4.0 mg·kg~(-1)was ig given, twice a day for three consecutive days and the alteration of cerebral blood flow was measured with laser Doppler flowmetry. Rotating acceleration equipment was used to provocate mouse vertigo for 30 min, and the spontaneous locomotor activities were tested for occurrence of vertigo in mice. Phencynonate hydrochloride 1.4-5.6 mg·kg~(-1)was ig given before rotating acceleration. Gastric phenol red emptying rate was used to determine the anti-nausea effect of the test drug in mice 30 min after phencynonate hydrochloride 1.4-8.4 mg·kg~(-1)was ig given. RESULTS The cerebral blood flow of the rat model with bilateral common carotid arteries occlusion was reduced significantly after 24 h(P<0.01). Compared with the model group, phencynonate hydrochloride(0.5, 2.0 and 4.0 mg·kg~(-1)) increased the cerebral blood flow in a dose-dependent manner in rats with cerebral ischemia(P<0.01). The spontaneous locomotor activities were significantly reduced after vertigo stimulation in mice(P<0.05).Compared with the model group, phencynonate hydrochloride(2.8 and 5.6 mg·kg~(-1)) increased the movement distance and speed of vertigo mice(P<0.05). Phencynonate hydrochloride(2.8, 5.6 and8.4 mg·kg~(-1)) inhibited the gastric emptying of mice(P<0.05). CONCLUSION Phecynonate hydrochloride can improve the cerebral blood flow and locomotor activities in vertigo rats, while inhibiting gastric emptying, which points to the therapeutic potential of phencynonate hydrochloride for vertigo in clinic.
引文
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[14]Wang JQ,Cai YL,Chen XM,Tao DY,Fu ZJ,Wang XL,et al.Screen of sea sickness behavior indices of simulated sea sickness in rats and observation of adaptability rules[J].Acad J Second Mil Med Univ(第二军医大学学报),2009,30(10):1119-1121.
[15]Shannon HE,Peters SC.A comparison of the effects of cholinergic and dopaminergic agents on scopolamine-induced hyperactivity in mice[J].J Pharmacol Exp Ther,1990,255(2):549-553.
[16]Zhong GX,Yan J,He QS.Advances in antimotion sickness drugs[J].Her Med(医药导报),2010,29(6):747-749.
[17]Gao X,Sun LN,Kong Z,Chen W,Guan ZL.Study progress of nausea and vomiting and their mechanism[J].Med Recapit(医学综述),2007,13(14):1043-1045.
[18]Li XA.Clinical observation on scopolamine acupoints applying to treat and prevent vomiting reaction of patients undergoing chemotherapy[J].Chin Nurs Res(护理研究),2007,21(8C):2213-2214.
[19]Li N,Tian ZB,Sun GR,Wei LZ,Xu L,Wang BH,et al.Effect of nesfatin-1 on gastric emptying and contraction of gastric smooth muscle strips in obese rats[J].World Chin J Digestol(世界华人消化杂志),2012,20(8):631-637.
[2]Jing GP,Tang JL.Cause and clinical manifestation of vertigo[J].Chin Gen Pract(中国全科医学),2009,12(3A):417-419.
[3]Sun XY,Ju Y,Zhao XQ.Research progress of posterior circulation ischemia[J].Chin J Stroke(中国卒中杂志),2011,16(10):839-843.
[4]Caplan L.Posterior circulation ischemia:then,now,and tomorrow.The Thomas Willis Lecture-2000[J].Stroke,2000,31(8):2011-2023.
[5]Hain TC,Uddin M.Pharmacological treatment of vertigo[J].CNS Drugs,2003,17(2):85-100.
[6]Spinks A,Wasiak J.Scopolamine(hyoscine)for preventing and treating motion sickness[J].Cochrane Database Syst Rev,2011,6:CD002851.
[7]Rascol O,Clanet M,Montastruc JL.Calcium antagonists and the vestibular system:a critical review of flunarizine as an antivertigo drug[J].Fundam Clin Pharmacol,1989,3(Suppl):79s-87s.
[8]Shi JX,Wang X.Research progress of flunarizine hydrochloride in clinical application[J].China Pract Med(中国实用医药),2007,2(20):80-82.
[9]Liu CG,Yun LH.A new central anticholinergic anti-motion sickness drug phencynonate hydrochloride[J].Chin J Pharmacol Toxicol(中国药理学与毒理学杂志),2005,19(4):311-320.
[10]Wang Y,Wang LY,Zheng JQ,Zhong BH,Liu H,Liu KL.Comparative studies of the pharmacological profiles between phencynonate hydrochloride and its derivatives[J].J China Pharm Univ(中国药科大学学报),2006,37(1):59-62.
[11]Zhang LL,Liu HQ,Yu XH,Zhang Y,Tian JS,Song XR,et al.The combination of scopolamine and psychostimulants for the prevention of severe motion sickness[J].CNS Neurosci Ther,2016,22(8):715-722.
[12]Chen XH,Tong L,Kang WJ,Weng YX.Effects of content variation of trace elements in traditional Tibetan medicine"Junxi"after processing on gastric emptying and intestinal propulsive in mice[J].Nat Prod Res Dev(天然产物研究与开发),2015,27:1811-1814,1835.
[13]Fu YB,Yang XD,Xu BL.A clinical study of the efficacy using xuanyunning and sibelium in treatment of vertigo caused by vertebrobasilar insufficiency[J].Pract J Cardiac Cereb Pneum Vasc Dis(实用心脑肺血管病杂志),2009,17(9):771-772.
[14]Wang JQ,Cai YL,Chen XM,Tao DY,Fu ZJ,Wang XL,et al.Screen of sea sickness behavior indices of simulated sea sickness in rats and observation of adaptability rules[J].Acad J Second Mil Med Univ(第二军医大学学报),2009,30(10):1119-1121.
[15]Shannon HE,Peters SC.A comparison of the effects of cholinergic and dopaminergic agents on scopolamine-induced hyperactivity in mice[J].J Pharmacol Exp Ther,1990,255(2):549-553.
[16]Zhong GX,Yan J,He QS.Advances in antimotion sickness drugs[J].Her Med(医药导报),2010,29(6):747-749.
[17]Gao X,Sun LN,Kong Z,Chen W,Guan ZL.Study progress of nausea and vomiting and their mechanism[J].Med Recapit(医学综述),2007,13(14):1043-1045.
[18]Li XA.Clinical observation on scopolamine acupoints applying to treat and prevent vomiting reaction of patients undergoing chemotherapy[J].Chin Nurs Res(护理研究),2007,21(8C):2213-2214.
[19]Li N,Tian ZB,Sun GR,Wei LZ,Xu L,Wang BH,et al.Effect of nesfatin-1 on gastric emptying and contraction of gastric smooth muscle strips in obese rats[J].World Chin J Digestol(世界华人消化杂志),2012,20(8):631-637.