Objective: To investigate whether RhoA/Rho-kinase contributes to the occurrence of chronic post-thoracotomy pain (CPSP) by up regulation of glutaminase 1 (GLS1) expression in the spinal dorsal cord.
Methods: Twenty five male Sprague Dawley (SD) rats were divided into control group (n=5) and model group (n=20). The rats in the model group were randomized into two sub groups (n=10) for observation on day 10 and day 21 after thoracotomy, and each group was further divided into CPSP and non CPSP groups according to the behavioral test results. All the rats were sacrificed after behavioral test for examination of GLS1 and RhoA expressions in the spinal cord using Western blotting and RT PCR. We also compared the effect of the Rho kinase inhibitor fasudil and saline, both injected intraperitoneally daily at 10 mg/kg for 7 consecutive days following thoracotomy, on CPSP and GLS1 expression in 30 male SD rats on day 21 after thoracotomy.
Results: Compared with the control group, the rats with CPSP showed significantly increased expressions of GLS1 and RhoA mRNA in the spinal cord on both day 10 and day 21 following thoracotomy (P<0.01), but the rats without CPSP did not show obvious changes in GLS1 and RhoA expressions. In fasudil treated rats, the mechanical pain threshold was obviously increased and the expressions of GLS1 and RhoA were significantly reduced as compared with those in saline treated rats (P<0.01).
Conclusion: RhoA plays an important role in the occurence of CPSP by up-regulating the expression of GLS1 in the spinal dorsal cord of rats.
目的: 探讨RhoA对大鼠开胸术后慢性疼痛发生的作用是否与其影响大鼠脊髓背根神经节中谷氨酰胺酶Ⅰ表达有关。
方法: 第1部分：验证谷氨酰胺酶Ⅰ和RhoA在脊髓背根神经节的表达。取25只雄性SD大鼠分为对照组（n=5）和模型组（n=20）；模型组依开胸术后第10天和第20天分为两组，并依据行为学测定的结果再分为术后慢性疼痛组和术后非慢性疼痛组，同时分别检测谷氨酰胺酶Ⅰ和RhoA的表达。因对照组不施行开胸手术，故只检测术前的表达水平。第2部分：研究RhoA激酶抑制剂法舒地尔对谷氨酰胺酶Ⅰ表达的影响。30只雄性SD大鼠随机分为法舒地尔组和非处理组。术毕缝皮后，法舒地尔组大鼠接受法舒地尔腹腔注射；非处理组注射等量生理盐水。术后第21天，根据行为学测试结果进行分组并检测谷氨酰胺酶Ⅰ及RhoA的表达水平。
结果: 与对照组相比，慢性疼痛组在第10天和第21天谷氨酰胺酶Ⅰ和RhoA的mRNA的表达量都有显著增加（P < 0.01）。然而，处理组和术后非慢性疼痛组的谷氨酰胺酶Ⅰ和RhoA的表达没有统计学差异。与法舒地尔组相比，非处理组的机械痛域显著降低。同时，与非处理组相比，法舒地尔组的谷氨酰胺酶Ⅰ和RhoA的表达量显著降低（P < 0.01）。
结论: RhoA通过上调脊髓背角中谷氨酰胺酶Ⅰ的表达在促进开胸术后慢性疼痛的发生中发挥了重要作用。