糖胃康防治糖尿病高脂血症大鼠的实验研究
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摘要
目的:
     研究中药复方糖胃康对糖尿病高脂血症的防治作用,并探讨其作用机制,为其临床应用和开发提供科学依据。
     方法:
     选用雄性Wistar大鼠48只,体重180~220g。将实验大鼠先稳定饲养一周,均经尿糖试纸检测为尿糖阴性。然后给予禁食12小时,以链脲佐菌素溶液溶于0.1mol/l柠檬酸-柠檬酸钠缓冲液(pH=4.5),配置成浓度为1%的溶液,按45mg/kg体重的剂量经腹腔一次性注射,注射后24h,36h,72h后分别检测大鼠非空腹尾静脉血糖值,选用血糖持续大于16.7mmol/L的大鼠36只,将其随机分为糖尿病高脂血症模型组、糖胃康小剂量治疗组、糖胃康大剂量治疗组,每组12只。另选12只健康大鼠为空白对照组,并以等量消毒生理盐水腹腔注射。空白对照组给予标准丸状鼠饲料规则喂养,其余各组均予高热量高脂饮食不规则喂养,即单日上午进食,双日下午禁食。各组大鼠均随意饮水。在实验期间观察记录进食量、进水量、尿量,每周测体重1次。各组均在造模同时开始灌胃给药,空白对照组及模型组给予15ml/kg剂量的生理盐水灌胃;糖胃康大剂量治疗组(48.00g/kg)按15ml/kg剂量灌胃;糖胃康小剂量治疗组(12.00g/kg)按15ml/kg剂量灌胃,每天1次,共4周,实验结束前一天记录大鼠体重和非空腹血糖值,末次给药后禁食24小时,眼球取血,测定TC、TG、LDL-C、HDL-C。断头处死。
     结果:
     造模3天后,模型组与治疗组出现明显多饮、多食、尿量增加,随后出现持续性多饮、多食、多尿、体重减轻,第2周时可见到食量明显减少、消瘦、精神倦怠、反应迟钝、皮毛疏松无光泽,个别口角、足背溃烂,下腹部潮湿、肮脏,尾巴尖由溃烂至发黑枯槁,最后断尾,并逐渐出现死亡。给药4周后,与空白组相比较,模型组大鼠一般情况差,消瘦懒动,饮食量少,无攻击性,易感染,存活率明显降低,血糖显著升高(P<0.01),体重显著降低(P<0.01),TC、TG、LDL-C显著升高(P<0.01),HDL-C显著降低(P<0.01)。提示链脲佐菌素和高脂高热量不规则饮食复合制备而成的糖尿病高脂血症动物模型造模成功。各药物治疗组与模型组比较,存活率依次为:模型组为8/12,糖胃康大剂量治疗组为10/12,糖胃康小剂量治疗组为9/12;治疗组与模型组比较血糖有所降低(P<0.05)。各治疗组与模型组比较,体重有所增加,其中糖胃康大剂量治疗组与模型组比较有显著性差异(P<0.01);从TC、TG、LDL-C看,糖胃康大剂量治疗组比模型组显著降低(P<0.01),糖胃康小剂量治疗组与模型组比较有差异(P<0.05);从HDL-C看,糖胃康大剂量治疗组比模型组显著升高(P<0.01),糖胃康小剂量治疗组与模型组比较有差异(P<0.05)。糖胃康大剂量组与小剂量组比较,血糖、TC、TG、HDL-C、LDL-C均存在显著差异(P<0.01)。提示,糖胃康有治疗糖尿病高脂血症的作用,而且呈一定的量-效关系。
     结论:
     本实验结果表明:①链尿佐菌素一次性大剂量腹腔注射配合高热量、高脂肪饲料喂养,可在较短时间内成功诱导出糖尿病高脂血症模型。②糖胃康有显著改善糖尿病高脂血症大鼠血糖、脂质代谢紊乱的作用。③糖胃康在改善糖尿病高脂血症大鼠血糖及脂质代谢紊乱方面呈现出一定的量-效关系。
Objective:
     To study the preventive and therapeutic effect of Tangweikang (TWK), a preparation of traditional Chinese medicine, to the Diabetic associated with hyperlipemia, and explore the mechanism and offer the scientific basis for TWK's clinic application and exploitation.
     Methods:
     36 Wister diabetic rats were randomly divided into three groups: model group, TWK low treatment group, TWK high treatment group, 12 rats in each group. The diabetic rats were induced by IP of STZ, 45mg/Kg and their blood sugar were continue higher than 16.7mmol/L. Further more choose another 12 healther rats as the normal control group. The control group was feed regularly on standard rats feed. The other three grouPs were fed on high calorie feed (high sugar and fat) irregularly. All the rats drunk water freely. During the experiment period, the appetite, water volume, urine volume, stool character should be observed, and weight the rats, test the urine sugar once every week. Each group was perfused stomach with drugs during establishing the model. The control group and the model group were perfused stomach with saline, 15ml/kg. TWK high does treatment group 15ml/kg (48.00g/kg). TWK low does treatment group 15ml/kg (12.00g/kg), once per day, lasted 4 weeks. Recorded the weight and the blood sugar on an un-empty stomach. The day before the last day, fasting 24h after the last feeding, the lever of TC、TG、HLD-C、LDL-C was measured.
     Result:
     3 days after establishing the models, rats of the model group and the treatment group got drink and eat more, urine volume increased, two weeks later the rats got to be poor appetite, lassitude and intertia, less stool, losing weight obviously than the control group. 4 weeks later, the rats of the model group were worse than the control group, emaciation, lazy to move, poor appetite, no aggressiveness and easy infection, survival rate sharply decreased; the rats of the model group compared with the control group, blood sugar significantly increased (P<0.01), weight obviously decreased, the levels of TC、TG、LDL-C significantly increased (P<0.01), HDL-C Sharply decreased (P<0.01). Each drug treatment group compared with the model group, the survival rate is respectively as followed: low and high does TWK treatment groups are 9/12 and 10/12. The blood suger decreased than the model group(P<0.05), weight increased, the high does TWK treatment group compared with the model group (P<0.01); as the TC、TG、LDL-C were concerned, low and high does TWK treatment groups decreased than the model group (P<0.05), as the HDL-C was concerned, the TWK high does treatment group significantly increased than the model group (P<0.01), the TWK low does treatment group increased compared with the model group(P<0.05).There is difference on the blood sugar、TC、TG、HDL-L、LDL-C between the high and low does of TWK treatment.group, it states that TWK is significant usage to the Diabetic associated with hyperlipemia with a certain does-effect relation.
     Conclusions:
     The Diabetic associated with hyperlipemia rats can be induced in a short time by injecting with STZ (45mg/kg) into their abdominal cavities and feeding them on high calorie and fat feed stuff. TWK is significant usage to the Diabetic associated with hyperlipemia with a certain does-effect relation.
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