糖尿病大鼠四肢痛阈及周围神经超微结构的变化

Dynamic observation of pain threshold and ultrastructural changes of peripheral nerves in diabetic rats

目的观察链脲佐菌素(STZ)诱导Ⅰ型糖尿病大鼠模型四肢痛阈的变化及背根神经节细胞和腓肠神经超微结构变化。方法6周龄清洁级雄性SD大鼠50只,随机分为对照组10只,模型组40只。模型组采用一次性腹腔注射60mg/kg体质量的链脲佐菌素(STZ)诱导Ⅰ型糖尿病大鼠模型,对照组予以等量生理盐水,监测两组大鼠体质量及血糖变化,并观察大鼠痛阈改变;模型组分别于造模成功后2,4,6周随机选取8只大鼠取背根神经节和腓肠神经,采用透射电镜观察超微结构变化。结果大鼠糖尿病造模成功率为82.5%,随周龄增加,糖尿病组大鼠体型明显消瘦,体质量与对照组相比差异具有统计学意义(P<0.05);造模成功后第2周糖尿病组的机械性痛阈即低于正常组,且随时间的延长,痛阈逐渐减低,两组间差异具有统计学意义(P<0.05)。随病程增加背根神经节细胞核膜皱缩逐渐加重,内质网逐渐出现水肿,空泡化;腓肠神经脱髓鞘病变也逐渐加重,与机械痛阈的降低存在一致性。结论单次腹腔注射STZ(60mg/kg)后可诱导出稳定的Ⅰ型糖尿病大鼠模型,且随病程增加,大鼠四肢痛阈降低逐渐加重,背根神经节细胞和腓肠神经超微结构病变也逐渐加剧。

Objective To observe the pain threshold and the ultrastructure of dorsal root ganglion cell and sural nerve in streptozotocin(STZ)-induced diabetic rats.Methods A total of 50 six-week-old male SD rats were randomly divided into control group(n=10)and model group(n=40).The mice in model group were intraperitoneally injected with STZ(Sigma,60 mg/kg body weight)to establish the diabetic model,while the mice in control group were given the same amount of saline.The changes of body weight,blood sugar and the mechanical withdrawal threshold(MWT)were monitored.Eight rats were randomly selected in model group after the successful modeling to observe the ultrastructural changes of dorsal root ganglion and sural nerve at weeks 2,4 and 6,respectively.Results All of the rats survived,and 82.5%rats had blood glucose more than 16.7 mmol/L.The body weight was significantly reduced in model group compared with control group at the same time point(P<0.05).MWT was lower in model group than in control group at the second week after the successful modeling(P<0.05),and it gradually decreased with the prolongation of time.With the development of diabetes,the shrinkage of nuclear membrane was aggravated gradually in the dorsal root ganglion,and the endoplasmic reticulum became edema and vacuolation gradually.In the sural nerve,the demyelinating lesions were also gradually aggravating,and the MWT was also decreased.Conclusion Stable typeⅠdiabetic rat model can be induced by single intraperitoneal injection of STZ(60 mg/kg).With the progression of the disease,the pain threshold and the ultrastructural changes of dorsal root ganglion cells and sural nerve are aggravated gradually in rats.