长期应用重组人睫状神经因子(rhCNTF)对谷氨酸钠肥胖大鼠血脂的影响

Antilipemic Effects of rhCNTF in Neonatally Monosodium Glutamate-Treated Obese Rats

目的研究长期应用rhCNTF对谷氨酸钠(MSG)肥胖大鼠血脂的影响。方法建立MSG肥胖大鼠模型。3月龄时将肥胖动物随机分5组:分别皮下注射rhCNTF300μg·kg-1·d-1(高剂量组)、100μg·kg-1·d-1(中剂量组)、30μg·kg-1·d-1(低剂量组);西布曲明灌胃8 mg·kg-1·d-1(阳性对照组);模型组和对照组均给予生理盐水1 mL·kg-1·d-1,连续给药33 d。末次给药后24 h,同时动物禁食过夜后,在水合氯醛麻醉下测体重、身长,计算LI;断头后取腹部脂肪称重计算脂肪系数;腹主动脉取血离心后测血清总胆固醇、甘油三酯、高密度脂蛋白、血糖和血清胰岛素水平。结果(1)造模:正常大鼠189.40±38.72 g,谷氨酸钠肥胖大鼠平均体重(246.72±36.67)g,(P<0.001);LI(Lee’s指数)分别为289.27±9.05和304.42±9.64(P<0.001),说明造模成功。(2)药物实验结果高、中剂量给药组LI、脂肪系数、血总胆固醇、甘油三酯、血糖明显下降,高剂量组胰岛素水平也有所下降,达到统计学要求的显著性。结论rhCNTF30～300μg·kg-1·d-1皮下注射连续用药33 d,对谷氨酸钠肥胖大鼠具有明显的降脂作用,可能对Ⅱ型糖尿病肥胖有效。

Objective To observe the antilipemic effects of recombinant human ciliary neurotrophic factor（rhCNTF） in the Neonatally Monosodium Glutamate-Treated Obesity model rats. Methods MSG obese rat model was established in rats by treatment with monosodium glutamate in the neonatal stage. The increases in the Lee＇s index （body weightl/3/ body length ） and in retroperitoneal fat as well as decreases in spontaneous motor activity were recorded. Food consumption and associated hypothalamic low body length obesity（monosodium glutamate-treated obesity; MSG-OB） were observed as these rats grew. Treatment with rhCNTF at 30 - 300μg·kg-1 s.e. once a day was given continuously for 33 days. The body weight and food intake were monitored every day. After final administration, rats were narcotized with choral hydrate, then the body length and weight were measured to calculate Lee＇s index. Blood was sampled through abdominal aorta to meature the serum levels of glucose and lipids. Fat around kidney and genitals and in abdominal cavity was collected for calculation of fat index. Results The body weight and Lee＇s index of MSG-rats significantly higher than that of normal rats, indicating that MSG-OB rats was established successfully. The long-term administration of high and middle dose of rhCNTF resulted in a significant and dose-dependent reduction of Lee＇s index, fat index, serum triglyceride （TG） and tatal cholesterol （TC）, and to profoundly increased high density lipoprotein- cholesterol （HDL-C） in comparison with obese saline-treated control. It also reduced a significantly the level of serum glucose hypoglycemic effect. Conclusion rhCNTF has significant and dose-dependen antilipemic effects in MSG-rats. Along with the antilipemic effect, rhCNTF also produces a significant hypoglycemic effect.