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目的研究短、长期应用rhCNTF对谷氨酸钠肥胖大鼠的减肥作用机制,为新药开发提供药理动物实验依据。方法建立谷氨酸钠(MSG)大鼠模型。3月龄时将肥胖动物随机分10组,长、短周期各5组分别给药。长周期连续给药33 d,短周期连续给药10 d。末次给药24 h后空腹断头,取生殖器周围同一部位小块脂肪组织经10%福尔马林固定后做光镜检查(400倍),取三个视野计数全视野脂肪细胞数并计算平均值;取空肠固定于电镜液,电镜扫描观察空肠绒毛密度及相对吸收表面积大小。结果 1)造模:正常大鼠体质量为(189.40±38.72)g,谷氨酸钠肥胖大鼠平均体质量为(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)药物实验结果中,短周期给药组:高、中剂量组脂肪细胞体积变小,高剂量组空肠绒毛密度下降,相对吸收面积减小(P<0.01或P<0.05);长周期给药:高、中剂量组脂肪细胞体积变小,空肠绒毛密度下降,相对吸收面积减小(P<0.01或P<0.05)。结论每天皮下注射rhCNTF 30～300μg/kg使谷氨酸钠肥胖大鼠的脂肪细胞变小,减肥作用与减小空肠绒毛膜吸收面积有关,作用呈剂量依赖性。
Objective To study the mechanism of weight loss of rhCNTF on short-term and long-term application of glutamate in obese rats, and to provide experimental basis for the development of new drugs. Methods A rat model of glutamate (MSG) was established. 3-month-old obese animals were randomly divided into 10 groups, long, short cycle of 5 groups were administered. Long-term continuous administration of 33 d, short-term continuous administration of 10 d. 24 hours after the last administration, the rats were sacrificed on the empty stomach and the small pieces of adipose tissue in the same area around the genital area were examined by light microscopy (400 times) after fixation with 10% formalin. The number of total visual fat cells Value; take jejunum fixed in the electron microscope liquid, electron microscopy scan jejunal villi density and relative absorption surface area size. The results were as follows: 1) The body weight of normal rats was (189.40 ± 38.72) g and that of glutamate-induced obesity rats was (246.72 ± 36.67) g, (P <0.001) 289.27 ± 9.05 and 304.42 ± 9.64 (P <0.001). Description modeling success. 2) In the drug experiment results, the short-period administration group showed that the volume of fat cells decreased in high and medium dose groups, the density of jejunum villi in high dose group decreased, and the relative absorption area decreased (P <0.01 or P <0.05) Medicine: The volume of fat cells in high and medium dose groups decreased, the density of jejunum villi decreased and the relative absorption area decreased (P <0.01 or P <0.05). Conclusion Subcutaneous injection of 30 ~ 300μg / kg rhCNTF subcutaneously daily reduced the fat cells of glutamate-induced obesity rats, and the weight-loss effect was related to the reduction of the absorption area of jejunum chorion in a dose-dependent manner.