背景:内脏-内脏之间存在广泛的伤害性传人会聚和相互作用.在跨器官痛觉过敏的发生中起重要作用。目的:在内脏高敏感状态下建立跨器官敏化大鼠模型,探讨蛋白激酶C1(PKCγ)对跨器官内脏敏感性的调控作用.方法:Sprague-Dawlev大鼠随机分为4组.其中3组在鸡卵清蛋白(OVA)基础致敏联合结直肠芥子油(MO)灌注建立结直肠-膀胱跨器官敏化模型的基础上,分别鞘内注射PKC叫特异性抑制剂GF109203X、0.9%NaCl溶液(NS)或不予鞘内注射,另一组为正常对照组。各组大鼠行梯度结直肠扩张/膀胱扩张(CRD/UBD).根据腹壁肌电活动曲线下面积(AUC)评估内脏敏感性的变化。结果:各组UBD梯度扩张刺激体积均与腹壁肌电活动AUC显著相关(P〈0.05)。UBD扩张体积为1.0、1.5、2.0m1以及CRD扩张压力为40、60、80mmHg时,OVA+MO组AUC显著高于正常对照组(P〈0.05);UBD扩张体积为1.5、2.0ml以及CRD扩张压力为60、80mmHg时,OVA+MO+GF109203X组AUC较OVA+MO+NS组显著降低(P〈0.05)。结论:鞘内注射PKC吖特异性抑制剂能逆转跨器官交叉内脏高敏感性,提示PKC7在跨器官敏化的产生和维持中起重要作用。
Background: Viscerovisceral convergence of nociceptive afferents and their interactions play an important role in the cross-organ hyperalgesia. Aims: To establish a cross-organ sensitization model in rats with visceral hypersensitivity, and to investigate the modulatory effect of protein kinase Cγ (PKCγ) on cross-organ visceral hypersensitivity. Methods: The Sprague-Dawley rats were randomly divided into four groups. Three groups received basal ovalbumin (OVA)- sensitization combined with colorectal mustard oil (MO) instillation to establish a colorectum-bladder cross-organ sensitization model, and then injected intratheeally with GF109203X, a specific inhibitor of PKCγ normal saline, and without intratheeal injection, respectively. One group served as normal controls. Gradient colorectal distention/urinary bladder distention (CRD/UBD) were conducted and the visceral sensitivity was evaluated by the area under curve (AUC) of myoelectrieal activity of abdominal wall muscle. Results: Significant correlation was found between the gradient distention volume of UBD and AUC of myoelectrical activity in all four groups (P〈0.05). AUC in rats received OVA combined with MO increased significantly at UBD volume of 1.0, 1.5, 2.0 ml and CRD pressure of 40, 60, 80 mm Hg when compared with the normal controls (P〈0.05). GF109203X intrathecal injection reduced significantly the increased AUC at UBD volume of 1.5, 2.0 ml and CRD pressure of 60, 80 mm Hg in rats received OVA combined with MO (P〈0.05). Conclusions: Intrathecal injection of specific inhibitor of PKCγ can reverse the cross-organ visceral hypersensitivity, which indicates that PKCγ, is involved in the development and maintenance of cross-organ sensitization.