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脱细胞牛心包与透明质酸钠联合应用预防术后心包粘连。

Combined application of acellular bovine pericardium and hyaluronic acid in prevention of postoperative pericardial adhesion.

机构信息

Department of Pediatric Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University, School of Medicine, Shanghai, China.

出版信息

Artif Organs. 2014 Mar;38(3):224-30. doi: 10.1111/aor.12140. Epub 2013 Nov 21.

Abstract

An experiment was designed to find the suitable acellular bovine pericardium (ABP) patch in pericardial cavity reconstruction and to evaluate the effect of sodium hyaluronic acid (NaHA) on inflammatory reaction in prevention of pericardial adhesions. The pericardial adhesion model was established in 20 rabbits, weighing from 3.2 to 3.6 kg. Groups were classified as follows: Group A (n = 5), the control group, the pericardium was directly closed; Group B (n = 5), 0.15% glutaraldehyde-treated ABP (low cross-link degree); Group C, 0.3% glutaraldehyde-treated ABP (middle cross-link degree); Group D, 0.15% glutaraldehyde-treated ABP + NaHA solution. Blood samples were collected at 6 h, 24 h, 3 days, and 5 days, to assay postoperative inflammatory reaction. The tenacity and severity of adhesions were evaluated 2 months after operation, by macroscopic and microscopic examinations, and Q-PCR (real-time quantitative polymerase chain reaction) test was used to quantitatively analyze the associated genes with adhesion. Pericardium regeneration was demonstrated by immunohistochemical technique to identify mesothelial cells. In Group D, the serum concentration of tumor necrosis factor-α (TNF-α) was significantly lower in the early postoperative period, and the mean adhesion score (adhesion between the epicardium and ABP) was significantly lower compared with the control group (Groups D vs. A: 0.20 ± 0.45 vs. 2.00 ± 0.71, P = 0.009*). The signs of degradation of the ABPs were observed 2 months postoperation in Groups D and B. Immunohistochemically, the positive cytokeratin AE1 staining results demonstrated the relatively total regeneration of the pericardium in Group D. Signs of regeneration were observed in Group D. Compared with the control group, the level of TGF-β2 in Group D was significantly lower (0.00132 ± 0.00114, P = 0.022*). The TGF-β3 level was statistically significant, being highest in Group D (0.00805 ± 0.00136, P = 0.029*). The mean quantity of Smad6 in Group D was also lower than the other groups. Low cross-link degree ABP may be an efficient physical block between the epicardium and the sternum and also an ideal scaffold for pericardial tissue regeneration, whereas combined use with NaHA may significantly reduce postoperative pericardial adhesions. The signal transduction pathway of transforming growth factor-β (TGF-β) and Smad6 may play a key role in the formation of pericardial adhesion.

摘要

一项实验旨在寻找适合于心包重建的去细胞牛心包(ABP)补片,并评估透明质酸钠(NaHA)在预防心包粘连中的抗炎作用。在 20 只体重 3.2-3.6kg 的兔子中建立心包粘连模型。将兔子分为 4 组:A 组(n=5),对照组,直接缝合心包;B 组(n=5),0.15%戊二醛处理的 ABP(低交联度);C 组,0.3%戊二醛处理的 ABP(中交联度);D 组,0.15%戊二醛处理的 ABP+NaHA 溶液。在术后 6h、24h、3d 和 5d 时采集血样,检测术后炎症反应。术后 2 个月通过大体和显微镜检查评估粘连的坚韧度和严重程度,并采用 Q-PCR(实时定量聚合酶链反应)检测定量分析与粘连相关的基因。采用免疫组化技术鉴定间皮细胞,以证明心包再生。在 D 组中,术后早期 TNF-α(肿瘤坏死因子-α)的血清浓度明显较低,与对照组相比,平均粘连评分(心外膜与 ABP 之间的粘连)明显较低(D 组 vs. A 组:0.20±0.45 vs. 2.00±0.71,P=0.009*)。术后 2 个月,D 组和 B 组观察到 ABP 降解迹象。免疫组化结果显示,D 组心包的阳性细胞角蛋白 AE1 染色结果表明心包的再生相对完全。在 D 组观察到再生迹象。与对照组相比,D 组 TGF-β2 水平明显较低(0.00132±0.00114,P=0.022*)。TGF-β3 水平也具有统计学意义,D 组最高(0.00805±0.00136,P=0.029*)。D 组 Smad6 的平均含量也低于其他组。低交联度 ABP 可能是心外膜和胸骨之间有效的物理阻隔,也是心包组织再生的理想支架,而与 NaHA 联合使用可能显著减少术后心包粘连。转化生长因子-β(TGF-β)和 Smad6 的信号转导通路可能在心包粘连形成中发挥关键作用。

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