目的 探讨负载罗哌卡因的聚已内酯多功能(PR)镇痛缝合线对小鼠腹部切口痛的影响。方法 SPF级健康雄性C57BL/6J小鼠32只,8~10周龄,体重20~27 g。采用随机数字表法将小鼠分为四组:假手术组(S组)、对照组(C组)、聚已内酯多功能镇痛缝合线组(P组)、PR镇痛缝合线组(PR组),每组8只。S组异氟醚麻醉后不进行手术操作; C组麻醉后制备腹部切口痛模型,以5-0外科缝合线行腹部切口缝合; P组造模并以聚已内酯缝合线行腹部切口缝合; PR组造模并以PR镇痛缝合线行腹部切口缝合。记录术后1—9 d的腹部机械敏感性(AMS)评分。于术后1、2 d进行糖水偏好实验。术后3 d麻醉后眼眶采血,检测血清肌酸激酶同工酶(CK-MB)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、肌酐(Cr)、C-反应蛋白(CRP)浓度。麻醉后处死小鼠,采用HE染色法评估皮肤组织和重要器官病理改变,免疫组织化学染色法测定皮肤组织TNF-α和IL-6含量,TUNEL法检测细胞凋亡水平。结果 与S组比较,C组和P组术后1、2、3、4 d的AMS评分明显升高(P<0.05),术后1 d糖水消耗百分比明显降低(P<0.05); C组、P组和PR组血清CRP浓度、皮肤组织TNF-α、IL-6含量和细胞凋亡率明显升高(P<0.05)。与C组比较,PR组术后1、2、3 d的AMS评分明显降低(P<0.05),术后1 d糖水消耗百分比明显升高(P<0.05);血清CRP浓度、皮肤组织TNF-α、IL-6含量和细胞凋亡率明显降低(P<0.05)。S组病理学检测未见炎性损伤改变,C组、P组和PR组见少量损伤和炎症。与C组比较,PR组皮肤局部炎症反应有所改善。结论 腹部切口痛模型验证PR镇痛缝合线长达3 d的镇痛作用,且不会引起局部和全身毒性反应。
Objective: To investigate the effect of polycaprolactone multifunctional analgesic suture loaded with ropivacaine (PR) on abdominal incision pain in mice.
Methods: Thirty-two SPF healthy male C57BL/6J mice, aged 8-10 weeks, weighing 20-27 g, were randomly divided into four groups using the random number table method: sham operation group (group S), control group (group C), polycaprolactone multifunctional analgesic suture group (group P), and PR analgesic suture group (group PR), eight mice in each group. No surgical operation was performed after isoflurane anesthesia in group S. The abdominal incision pain model was prepared, and abdominal incision suture was performed with a 5-0 surgical suture after anesthesia in group C. Group P was modeled and abdominal incision suturing was performed with polycaprolactone sutures. Group PR was modeled and abdominal incision suturing was performed with PR analgesic sutures. The abdominal mechanical sensitivity (AMS) scores were recorded on postoperative days 1-9. The sucrose preference experiment was conducted on postoperative days 1 and 2. The blood was collected from the orbit after anesthesia to detect the serum concentrations of creatine kinase-MB isoenzyme (CK-MB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (Cr), C-reactive protein (CRP) on postoperative day 3. The mice were sacrificed after anesthesia, and HE staining of skin tissues and important organs was performed to evaluate the pathological changes. The contents of TNF-α and IL-6 in skin tissues were determined by immunohistochemical staining. The level of apoptosis was detected by TUNEL method.
Results: Compared with group S, the AMS scores were significantly increased on postoperative days 1, 2, 3, and 4 (P < 0.05), and the percentage of sugar water consumption was significantly decreased in groups C and P on postoperative day 1 (P < 0.05). Compared with group S, the serum CRP concentration, the contents of TNF-α and IL-6 in skin tissue and the apoptosis rate were significantly increased in groups C, P, and PR (P < 0.05). Compared with group C, the AMS scores in group PR were significantly decreased on postoperative days 1, 2 and 3 (P < 0.05), and the percentage of sugar water consumption was significantly increased on postoperative day 1 (P < 0.05). Compared with group C, the serum CRP concentration was significantly decreased, and the contents of TNF-α and IL-6 in the skin tissue and the apoptosis rate were significantly decreased in group PR (P < 0.05). Pathological examination in group S showed no inflammatory injury changes, while a small amount of injury and inflammation were observed in groups C, P, and PR. Compared with group C, the local inflammatory response of skin in group PR was improved.
Conclusion: The abdominal incision pain model verified the analgesic effect of the PR analgesic suture for up to 3 days, and did not cause local and systemic toxic reactions.