To explore the role of vascular endothelial growth factor (VEGF) in diabetic peripheral neuropathic pain in rats. Methods: Twenty-four adult male Sprague-Dawley rats aged 8 weeks were randomly divided into 3 groups (n=8 per group). The control group (C group): rats were intraperitoneally injected with sodium citrate solution at 10 mL/kg; the model group (M group): rats were intraperitoneally injected with streptozotocin at 65 mg/kg; the treatment group (T group): rats received intraperitoneal injection of anti-VEGF antibody (10 mg/kg) at the 1st, 3rd, 7th, 10th day after STZ treatment. Meanwhile, rats of C and M group were received with the same volume of sodium citrate solution. Blood glucose was measured before 1 day or at the 1st, 3rd, 7th or 14th day after receiving STZ. Body weight, paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured before 1 day or at the 1st, 3rd, 5th, 7th, 10th or 14th day after receiving STZ. All lumbar spinal cords were dissected to examine the p-protein kinase B (p-Akt) and transient receptor potential vanilloid 1 (TRPV1) expression by Western blot. Results: After injection with STZ, the body weight showed significant differences at some time point between the M, T or C group (P<0.01); body weight of rat in the C group were increased gradually. Compared with the C group, the fast blood glucose in the M or the T Group at the same time points were increased significantly (P<0.01). The PWMT and PWTL of the M, T or C group were significant difference among various time points (P<0.01). The PWMT and PWTL in the M or T group were obviously reduced compared with those in the C group (P<0.01). Compared with the M group, the PWMT and PWTL in the T group were increased at the 10th or 14th day (P<0.01 or P<0.05). Compared with the C group, the p-Akt and TRPV1 levels in the M and T group were increased (P<0.01). Compared with the M group, p-Akt and TRPV1 levels in T group were decreased (P<0.01). Conclusion: VEGF is able to regulate the expression of TRPV1 through PI3K/Akt pathway, which contributes to diabetic peripheral neuropathic pain in rats. Anti-VEGF treatment may be useful for alleviation of diabetic peripheral neuropathic pain.
目的：探讨血管内皮生长因子(vascular endothelial growth factor，VEGF)在大鼠糖尿病周围神经痛(diabetic peripheral neuropathic pain，DPNP)发病机制中的作用。方法：24只8周Sprague-Dawley雄性大鼠，随机分为3组，每组8只：对照组(C组)，单次腹腔注射柠檬酸钠溶液10 mL/kg；模型组(M组)，单次腹腔注射链脲佐菌素(streptozotocin，STZ)65 mg/kg；干预组(T组)，单次腹腔注射STZ 65mg/kg建立模型，且在造模后第1，3，7，10天分别单次腹腔注射抗VEGF抗体10 mg/kg。C组和M组分别在相同时间点腹腔注射等体积柠檬酸钠溶液。注射STZ前1 d(基础值)、注射STZ后第1，3，7，14天检测大鼠空腹血糖值；注射STZ前1 d、注射STZ后第1，3，5，7，10，14天分别测定大鼠体重及后足机械痛阈和热痛阈；应用Western印迹法测定腰段脊髓磷酸化蛋白激酶B(phospho protein kinase B，p-Akt)和瞬时受体电位香草酸亚型1(transient receptor potential vanilloid 1，TRPV1)的蛋白表达。结果：注射STZ后，M组及T组大鼠与C组大鼠各时间点体重差异有统计学意义，C组大鼠体重增加(P<0.01)。与C组大鼠相同时间点比较，M组及T组大鼠空腹血糖升高(P<0.01)。3组大鼠足底机械缩足反射阈值(paw withdraw mechanical threshold，PWMT)和足底皮肤热刺激缩足反射潜伏期(paw withdraw thermal latency，PWTL)随时间变化差异有统计学意义(P<0.01)，与C组相同时间点比较，M组(第3，5，7，10，14天)及T组(第5，7，10，14天)PWMT和PWTL降低(P<0.01)。与M组比较，T组大鼠第10和14天PWMT和PWTL升高(P<0.01或P<0.05)。与C组比较，M组和T组大鼠脊髓p-Akt和TRPV1表达升高(P<0.01)；与M组比较，T组大鼠p-Akt和TRPV1表达降低(P<0.01)。结论：VEGF可能通过磷脂酰肌醇-3-激酶/蛋白激酶B(phosphatidylinositol 3-kinase/protein kinase B，PI3K/Akt)信号通路调控TRPV1的表达参与大鼠DPNP，抗VEGF治疗可能成为DPNP治疗的靶点之一。.