Abstract:  Objective This study was designed to investigate the anti—obesity mechanism of recombinant human ciliary neurotrophic factor(rhCNTF)in the Neonatally Monosodium Glutamate—Treated Obesity model rats and to provide the experiment data for the development of rhCNTF as a new drug．Methods MSG rat model was established in rats by treatment with monosodium glutamate in the neonatal stage．Treatment with rhCNTF at 30～ 300 Ixg·kg～s．c．once a day continuously for 10 or 33 days．The body weight and food intake were monitored every day．After final administration，rats were narcotized with choral hydrate，fat around genital was collected．Size of lipocytes was measured with the microscope．The density of jejunum villi was measured by means of electro— microscopic scan technique．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 short—term and long-term administrationof high and middle dose of rhCNTF resulted in a significant and dose—dependent reduction of size of lipocytes． Electromicroscopic scan displayed that the density of jejunum villi in MSG—rats receiving high and middle doses of rhCNTF on a long—term medication basis was markedly diminished，but not on a short-term use of rhCNTF seemed to be related to weakened intestinal absorption of nutritive substances as a result of decreased relative absorption area． Conclusion rhCNTF by SC route of administration has significant and dose--dependent anti--obesity effects in MSG-- rats．The anti-obesity effect of rhCNTF may be related to its anorectic property and its unfavorable effect on intestinal absorption of nutritive substances due to the reduced absorption area．

Key words: recombinant human ciliary neurotrophic factor(rhCNTF), MSG—rats；anti·obesity effect, density of iejunum villi

摘要： 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 4-9．64 (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 30～300 Ixg／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。

关键词: 重组人睫状神经因子, 谷氨酸钠肥胖大鼠, 减肥作用, 绒毛密度