益气活血凝胶贴片对糖尿病周围神经病变大鼠的治疗作用及安全性评价

Therapeutic effect and safety evaluation of Yiqi Huoxue Gel Patch on diabetic peripheral neuropathy

目的:对制备的益气活血凝胶贴片进行临床前安全性评价,并考察其对DPN大鼠的治疗作用。方法:取健康家兔、健康豚鼠以及正常Wistar大鼠,考察益气活血凝胶贴片皮肤给药后对家兔皮肤刺激性、豚鼠皮肤过敏性、大鼠急性毒性的影响,评价益气活血凝胶贴片皮肤用药安全性。取成年雄性Wistar大鼠,分为正常组及造模组,造模组大鼠采用高脂饲料加链脲佐菌素诱导建立DPN模型;将造模成功的大鼠随机分为3组:模型组、益气活血凝胶贴片低剂量组和高剂量组,正常组作为空白对照组,空白对照组及模型组大鼠给予凝胶基质,益气活血凝胶贴片组大鼠给予低剂量及高剂量益气活血凝胶贴片干预,每天给药1次,连续干预14 d;末次干预后,对各组大鼠进行感觉神经及运动神经传导检测,考察益气活血凝胶贴片对DPN大鼠运动神经及感觉神经的潜伏期及传导速度的作用。结果:益气活血凝胶贴片给药后对健康家兔皮肤无刺激性,对健康豚鼠皮肤无过敏性,对大鼠无急性毒性;与DPN模型组大鼠相比,益气活血凝胶贴片低剂量及高剂量组大鼠感觉神经、运动神经潜伏期明显缩短(P<0.05,P<0.01),传导速度明显升高(P<0.05,P<0.01)。结论:益气活血凝胶贴片皮肤用药安全性高,对大鼠DPN有改善作用,研究结果为该贴片的应用与开发奠定了重要基础。

Objective:To evaluate the pre-clinical safety of the prepared Yiqi Huoxue Gel Patch and to investigate its therapeutic effect on diabetic peripheral neuropathy rats.Methods:Healthy rabbits,guinea pigs and normal Wistar rats were selected to investigate the effect of Yiqi Huoxue Gel Patch on skin irritation in rabbits,skin irritability in guinea pigs and acute toxicity in rats after administration,and to evaluate the safety of Yiqi Tongluo Gel Patch on skin.Adult male Wistar rats were divided into normal group and model group.The rats in model group were induced by high-fat diet and streptozotocin to establish a model of diabetic peripheral neuropathy.The rats in model group were randomly divided into 3 groups:model group,Yiqi Huoxue Gel Patch low-dose and high-dose groups.The normal group was used as the blank control group,and the rats in the blank control group and model control group were given gel matrix,the rats in the Yiqi Huoxue Gel Patch groups were treated with low-dose and high-dose Yiqi Huoxue Gel Patch,once a day for 14 consecutive days.After the last intervention,the sensory nerve and motor nerve conduction of rats in each group were tested to investigate the effect of Yiqi Huoxue Gel Patch on the latency and conduction velocity of motor nerve and sensory nerve in rats with diabetic peripheral neuropathy.Results:Yiqi Huoxue Gel Patch had no irritation to the skin of healthy rabbits,no allergy to the skin of healthy guinea pigs and no acute toxicity to rats.Compared with the model group,the latencies of sensory nerve and motor nerve in Yiqi Huoxue Gel Patch low-dose and high-dose group were significantly shortened,and the conduction velocities were significantly increased.Conclusion:Yiqi Huoxue Cel Patch is safe for skin use and can improve diabetic peripheral neuropathy in rats.The research results provided an important foundation for the application and developmentof this patch.