通过局部注射转化生长因子β1中和抗体加速胃溃疡伤口愈合

Acceleration of wound healing in gastric ulcers by local injection of neutralising antibody to transforming growth factor beta 1.

作者信息

Ernst H, Konturek P, Hahn E G, Brzozowski T, Konturek S J

机构信息

Department of Medicine, University of Erlangen-Nuremberg, Germany.

出版信息

Gut. 1996 Aug;39(2):172-5. doi: 10.1136/gut.39.2.172.

DOI:10.1136/gut.39.2.172

PMID:8991853

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1383293/

Abstract

BACKGROUND

Application of neutralising antibodies (NAs) to transforming growth factor beta 1 (TGF beta 1) improves wound healing in experimental glomerulonephritis and dermal incision wounds. TGF beta 1 has been detected in the stomach, but despite the fact that this cytokine plays a central part in wound healing no information is available to determine if modulation of the TGF beta 1 profile influences the healing of gastric ulcers. This study examines gastric ulcer healing in the rat after local injection of NAs to TGF beta 1.

METHOD

Chronic gastric ulcers were induced in Wistar rats by the application of 100% acetic acid to the serosal surface of the stomach. Immediately after ulcer induction and on day 2, NAs to TGF beta 1 (50 micrograms), TGF beta 1 (50 ng), saline or control antibodies (IgG; 50 micrograms) were locally injected into the subserosa. Controls received no subserosal injections. Animals were killed on day 5 or 11, the ulcer area was measured planimetrically, sections were embedded in paraffin wax, and stained with trichrome or haematoxylin and eosin. Depth of residual ulcer was assessed on day 11 by a scale of 0-3, the percentage of connective tissue was determined by a semiquantitative matrix score and granulocytes and macrophages in the ulcer bed were also assessed.

RESULTS

The application of NAs to TGF beta 1 led to a significant acceleration of gastric ulcer healing on day 11 (0.6 (SD 0.8) v 3.7 (SD 2.6) mm2), a reduction in macrophages (23.7 (SD 22.6) v 38 (26) per 40 x power field) and granulocytes (8.5 (SD 5.6) v 20 (10) per 40 x power field), fewer histological residual ulcers (mean 1 (SD 0.9) v 2 (1.1)), a reduced matrix score, and a regenerative healing pattern. Excessive scarring was seen in the TGF beta 1 treated group.

CONCLUSION

Further treatment of gastric ulcers may induce a new treatment modality by local injection of NA to TGF beta 1 in an attempt to accelerate and improve ulcer healing.

摘要

背景

应用转化生长因子β1（TGFβ1）中和抗体可改善实验性肾小球肾炎和皮肤切口伤口的愈合。已在胃中检测到TGFβ1，尽管这种细胞因子在伤口愈合中起核心作用，但尚无信息确定TGFβ1水平的调节是否会影响胃溃疡的愈合。本研究检测了向大鼠局部注射TGFβ1中和抗体后胃溃疡的愈合情况。

方法

通过将100%乙酸涂抹于Wistar大鼠胃浆膜表面诱导慢性胃溃疡。在诱导溃疡后立即以及第2天，将TGFβ1中和抗体（50微克）、TGFβ1（50纳克）、生理盐水或对照抗体（IgG；50微克）局部注射到浆膜下。对照组不进行浆膜下注射。在第5天或第11天处死动物，用面积测量法测量溃疡面积，将切片用石蜡包埋，并用三色染色法或苏木精-伊红染色。在第11天通过0-3级评分评估残余溃疡的深度，通过半定量基质评分确定结缔组织的百分比，并评估溃疡床中的粒细胞和巨噬细胞。

结果

在第11天，应用TGFβ1中和抗体可显著加速胃溃疡愈合（0.6（标准差0.8）对3.7（标准差2.6）平方毫米），减少巨噬细胞数量（每40倍视野23.7（标准差22.6）对38（26）个）和粒细胞数量（每40倍视野8.5（标准差5.6）对20（10）个），减少组织学上的残余溃疡数量（平均1（标准差0.9）对2（1.1）个），降低基质评分，并呈现再生性愈合模式。在TGFβ1治疗组中观察到过度瘢痕形成。