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Prevention of Postoperative Adhesions with N, O-carboxymethyl Chitosan in Rabbit: A Large-sample Gross and Histopathological Observation
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摘要:
目的 评价羧甲基壳聚糖(N, O-carboxymethyl chitosan, NOCC)预防兔手术后粘连的效果。 方法 220只雌性大耳白兔采用双子宫模型造成手术粘连, 随机分组后接受单纯造模手术(对照组)或造模手术+关腹前腹腔内注射NOCC(NOCC组)。所有手术均由同一位术者完成。每组各22只大耳白兔在实验设计的5个观察时间点(术后3、7、14、28和42 d)分别被处死并评估其粘连情况, 包括范围、类型和强度等大体情况和炎症、纤维化以及新生血管等镜下情况。 结果 NOCC组在术后3 d时其粘连的范围(P=0.0337)和强度(P=0.0271)以及炎症反应情况(P < 0.0001)均显著轻于对照组。在术后14 d内, NOCC组的纤维化情况均明显轻于对照组(P均 < 0.0005)。与对照组相比, NOCC组的粘连强度在术后14、28、42 d均明显减轻(P均 < 0.05), 而其粘连类型评分在术后28和42 d也明显降低(P均 < 0.05)。 结论 经NOCC处理后, 兔盆腹腔术后粘连大体和病理学评分均不同程度降低。应用NOCC可有效预防盆腹腔术后粘连。 Abstract:Objective To assess the effect of N, O-carboxymethyl chitosan (NOCC) in preventing postoperative adhesion in a rabbit model. Methods Double uterine horn model was established in 220 female rabbits to induce postoperative adhesion. The rabbits were randomized to receive either adhesion-inducing operation only (control group) or adhesion-inducing operation + intraperitoneal injection of NOCC before closure (NOCC group). All the operations were performed by one operator. Twenty-two rabbits from each group were euthanized at one of the five different time points (postoperative day 3, 7, 14, 28, and 42), and adhesion formation was scored both grossly (extent, type, and tenacity) and histopathologically (inflammation, fibrosis, and vascularization). Results The extent (P=0.0337) and tenacity of adhesion (P=0.0271) as well as inflammation(P < 0.0001) were lower in the NOCC group than in the control group on day 3. Fibrosis was less obvious in the NOCC group compared to the control group (P < 0.0005) before day 14. The tenacity scores of adhesion on day 14, 28, and 42 were significantly lower in the NOCC group than in the control group(all P < 0.05), while the type scores were obviously lower in the NOCC group on day 28 and 42(all P < 0.05). Conclusions Treatment with NOCC could reduce both gross and histopathological scores of surgery-induced abdominopelvic adhesions in rabbits. NOCC could be an effective therapy for preventing postoperative abdominopelvic adhesion. -
图 1 大耳白兔双子宫造模手术后盆腹腔粘连的大体观察
因两组变化趋势相似，故A~D均展示对照组大体所见；A.术后3 d对照组：子宫和膀胱间的疏松、膜状粘连；B.术后7 d对照组：可见1例新生血管(箭头)；C.术后28 d对照组：新生血管网形成(箭头)；D.术后42 d对照组：粘连范围较28 d降低；E.术后42 d NOCC组:粘连更疏松，新生血管更细NOCC：羧甲基壳聚糖
图 2 大耳白兔双子宫造模手术后盆腹腔粘连的病理表现(HE染色，×150)
A.术后3 d对照组：可见微脓肿(箭头)；B.术后7 d对照组：可见新生微毛细管(箭头)；C.术后28 d对照组：可见一条有完整结构的大毛细血管，在其下方可见慢性炎症细胞浸润(箭头)；D.术后42 d对照组：纤维密度增加; E.术后42 d NOCC组：新生血管与术后28 d相似NOCC：同图 1
表 1 NOCC组和对照组在术后5个时间点的大体粘连评价情况
术后时间(d) 粘连特征 对照组[M(Q1, Q3)] NOCC组[M(Q1, Q3)] P 3 范围 2 (1，2) 1 (1，2) 0.0337 类型 2 (2，2) 2 (2，2) 0.7638 强度 2 (1.25，2) 1 (1，2) 0.0271 7 范围 2 (1，2) 2 (1，2) 0.4257 类型 2 (2，2) 2 (1.25，2) 0.4609 强度 2 (1.25，2) 1 (1，2) 0.1026 14 范围 2 (1，2) 1.5(1，2) 0.4693 类型 2 (2，1) 2 (1，2) 0.1142 强度 2 (1，2.75) 1 (1，2) 0.0410 28 范围 2.5(1，2) 2 (1.25，2) 0.5006 类型 2 (2，2) 2 (1，2) 0.0210 强度 2 (2，2) 1 (1，1) ＜0.0001 42 范围 2 (1，2) 1 (0，1) 0.1475 类型 2 (1，2) 1 (0，1) 0.0027 强度 2 (1，2) 1 (0，1) 0.0002 NOCC：同图 1 
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表 2 NOCC组和对照组在术后5个时间点的镜下粘连评价情况
术后时间(d) 镜下所见 对照组[M(Q1, Q3)] NOCC组[M(Q1, Q3)] P 3 炎症反应 5 (4, 6) 3(1, 3.75) ＜0.0001 纤维化 4 (3, 4) 3(2, 3) 0.0004 血管增生 0 (0, 0) 0(0, 0) 1.0000 7 炎症反应 2 (1, 3) 2(0, 4) 0.9044 纤维化 3 (3, 3.75) 1(1, 2) ＜0.0001 血管增生 2 (2, 4.75) 2(2, 3) 0.2717 14 炎症反应 1 (0.25, 2) 1(0, 1) 0.8226 纤维化 3 (3, 4) 2(0.25, 2.75) 0.0002 血管增生 4 (1.25, 5) 2(1, 3.75) 0.1012 28 炎症反应 0 (0, 1) 1(0, 2) 0.1468 纤维化 3 (3, 3.75) 3(2, 3) 0.4036 血管增生 2.5(2, 4) 3(2, 3) 0.8155 42 炎症反应 0 (0, 1) 1(0, 1) 0.4109 纤维化 3 (2.25, 4) 2(2, 3) 0.0501 血管增生 4 (2, 4.75) 3(2, 3) 0.2626 NOCC：同图 1
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