鞘内给予蛋白激酶Cγ基因短发夹RNA慢病毒载体对骨癌痛大鼠痛觉的影响

Effect of analgesia by intrathecal injection of PKCγ-shRNA lentivirus in rat model of bone cancer pain

目的 观察鞘内注射蛋白激酶Cγ（PKCγ）基因短发夹RNA（shRNA）慢病毒载体pLV-PKC2对骨癌痛大鼠痛觉的影响,探讨PKCγ基因shRNA对骨癌痛的镇痛效果.方法 选取成年雌性Wistar大鼠24只,随机分为四组：PKC组、骨癌痛组（CIBP组）、磷酸缓冲液组（PBS组）和对照组（C组）,每组6只.于骨癌痛模型制作前1 d、模型制作后每隔3天测定大鼠机械缩爪阈值和机械缩爪持续时间.使用免疫组织化学法检测大鼠脊髓背角PKCγ的表达.结果 PKC组大鼠鞘内注射慢病毒载体pLV-PKC2模型制作12 d后,各时点机械缩爪阈值较CIBP、PBS、C组明显升高;持续时间明显缩短（P〈0.05）.PKC组大鼠脊髓背角PKCγ蛋白表达量显著低于CIBP组（P〈0.05）.结论 慢病毒pLV-PKC2能明显降低骨癌痛大鼠脊髓背角PKCγ的蛋白表达量,同时具有显著的镇痛效应.

Objective To investigate the analgesic effect of intrathecal injection of protein kinase C garnma（PKCT）-short hair（sh）RNA lentivirus in rats with cancer-induced bone pain（CIBP）. Methods After establishernent of rats CIBP model, 24 female Wistar rats were randomly divided into PKC group, CIBP group, PBS group and Control group with 6 rats each. The changes of nociceptive behaviors including mechanical withdrawal threshold（MWT） and mechanical withdrawal duration（MWD） were assessed before injection and every other 3 days after injection. After completion of pain assessments, the rats were sacrificed and the spinal cord of [urnhar 4-6 segments was taken for detecting the expression of PKC~＇ by irnmunohistochemistry. Results The MWT of PKC group significantly increased and the MWD evidently prolonged compared to CIBP, PBS, C group on the 5th day after injection of lentivims pLV-PKC2 （the12th day after establishement of model）. The PKC7 expression in PKC group significantly reduced compared to that in CIBP group（P〈0. 05）. Conclusion Lentivims pLV-PKCe can both evidently decrease the expression of PKC2 and significantly produce analgesic effect.