摘要目的 研究TRPV1拮抗剂辣椒卓平(CPZ)作用于伏核对大鼠体质量及脂肪积累的影响,探讨其对神经病理性肥胖的治疗作用. 方法 40只SD大鼠采用随机数字表法分为5组,每组8只,分别为:对照组,不作任何处理；A组,伏核注射CPZ 1 nmol/mL;B组,伏核注射CPZ 10nmol/mL;C组,偏离伏核靶点注射CPZ 10 nmol/mL;D组,背侧纹状体内注射CPZ 10 nmol/mL;后4组注射剂量为1 μL,每侧每天1次,连续给药3d.观察注射后1周及3周大鼠体质量相对于对照组的变化及各组大鼠体质量增长速度的变化；解剖各组大鼠观察其体脂含量. 结果 A组大鼠在给药1周后体质量为起始体质量的(126.31±10.25)％,B组大鼠给药1周后体质量为起始体质量的(115.87±13.90)％,2组大鼠均较对照组大鼠(148.78±6.98)％的增幅明显降低,差异均有统计学意义(P＜0.05).给药3周后B组大鼠体质量为起始体质量的(132.82±15.8)％,仍较对照组大鼠(164.86±6.34)％的增幅明显降低,差异有统计学意义(P＜0.05).给药1周后A、B组大鼠平均每日体质量增长(3.2±0.78)g和(3.2±0.53)g,较对照组(10.26±1.76)g明显降低,差异有统计学意义(P＜0.05).给药3周后B组大鼠平均每日体质量增长(5.46±0.94)g,仍然低于对照组(10.33±1.37)g,差异有统计学意义(P＜0.05).解剖结果显示B组大鼠体脂含量明显低于对照组,差异有统计学意义(P＜0.05). 结论 CPZ拮抗伏核TRPV1受体对大鼠体质量增长及脂肪积累有较明显的抑制性中枢调节作用.TRPV1拮抗剂有可能成为理想的特异性神经病理性肥胖的治疗药物.

abstractsObjective To study the effect of administration of transient receptor potential vanilloid 1 (TRPV1) antagonist capsazepine (CPZ) into the nucleus accumbens (NAc) on the regulation of body weight and fat accumulation in rats, and evaluate the therapeutic effect of CPZ on neuropathic obesity. Methods Forty rats were randomly divided into 5 groups (n=8), namely, control group (without giving any treatment),group A (performed intra-NAc injection of 1 nmol/mL CPZ),group B (performed intra-NAc injection of 10 nmol/mL CPZ),group C (performed injection of 10 nmol/mL CPZ via the areas adjacent to NAc) and group D (performed injection of 10 nmol/mL CPZ via the dorsal striatum); rats of the later 4 groups were given 1 μL CPZ daily for a consecutive 3 d.The body weight of rats from different treatment groups 1 and 3 weeks after the injection was measured and compared them to that of the control group.Then,the animals were sacrificed,the body fat content of each group was evaluated. Results The body weight in rats of group A 1 week after the injection increased (126.31± 10.25)％ as compared with their original weight, and that in rats of control group increased (148.78±6.98)％ as compared with their original weight, which showed significant difference between the 2 increment (P＜0.05); the body weight in rats of group B 1 week after the injection increased (115.87± 13.90)％ as compared with their original weight, which showed significant decrease as compared with that in the control group (P＜0.05); The body weight in rats of group B 3 week after the injection increased (132.82±15.8)％ as compared with their original weight, and that in rats of control group increased (164.86±6.34)％ as compared with their original weight,which showed significant difference between the 2 increment (P＜0.05).Furthermore,the body fat content in group B was significantly lower than that of other groups (P＜0.05). Conclusion Blockade of NAc TRPV1 receptor by CPZ has significant inhibitory central adjusting effect on body weight and fat content in rats; and TRPV1 antagonist may potentially serve as a specific drug for neuropathic obesity.