Weinzweig J, Levenson S M, Rettura G, Weinzweig N, Mendecki J, Chang T H, Seifter E
Department of Biochemistry, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York 10461.
Ann Surg. 1990 Mar;211(3):269-76.
To test our hypothesis that supplemental vitamin A would mitigate the impaired healing that occurs in tumor-bearing animals, six groups of C3H mice, eight per group, eating a standard commercial mouse chow ad libitum that supports normal growth, reproduction, and longevity were innoculated with 200,000 C3HBA cells. When tumors measured approximately 6 mm in diameter, the mice were anesthesized and wounded (dorsal skin incisions and subcutaneous polyvinyl alcohol sponges). Twenty-four hours later, two groups (one continued on the chow and the other started on the chow supplemented with 150,000 IU vitamin A/kg chow) underwent local tumor irradiation; two groups, one ingesting the chow, the other the vitamin A supplemented chow, were started on cyclophosphamide therapy; two groups, one ingesting the chow, the other the vitamin A supplemented chow, received neither local tumor irradiation nor cyclophosphamide therapy. An additional two groups ingesting the chow, one group neither innoculated with tumor nor wounded, the other wounded by not innoculated, served as controls. Wound breaking strength and sponge reparative collagen accumulation (assessed by hydroxyproline proline measurement) were used as indicators of wound healing. The mice were killed 12 days after wounding. Tumor presence decreased wound breaking strength and sponge hydroxyproline content; these effects were largely negated by supplemental vitamin A. Local tumor irradiation diminished the adverse effect of tumor on sponge reparative collagen content but to a lesser extent than the supplemental vitamin A. Supplemental vitamin A added to the irradiation effect on healing but irradiation did not add to the vitamin A effect. Cyclophosphamide, a systemic radiomimetic anti-tumor agent, did not alter the impaired wound healing of the tumor-bearing mice. Supplemental vitamin A mitigated the impaired wound healing in the cyclophosphamide-treated tumor-bearing mice. Supplemental vitamin A also moderated the effects of wounding, tumor, and tumor therapies (local irradiation and cyclophosphamide) on the increase in adrenal size, leukopenia, thrombocytopenia, and thymic involution (except the last was not moderated in the cyclophosphamide-treated tumor-bearing rats). The splenic enlargement in the untreated tumor-bearing wounded rats and in those treated with cyclophosphamide was lessened by supplemental vitamin A. We hypothesize that these anti-stress effects of vitamin A underlie, in part, its action in mitigating the impaired wound healing of tumor-bearing mice, including those treated by local irradiation or cyclophosphamide. These findings have implications for the care of patients with malignant tumors.
为了验证我们的假设，即补充维生素A可减轻荷瘤动物出现的愈合受损情况，将六组C3H小鼠（每组8只）自由采食支持正常生长、繁殖和长寿的标准商业鼠粮，然后接种200,000个C3HBA细胞。当肿瘤直径约为6毫米时，对小鼠进行麻醉并致伤（背部皮肤切口和皮下植入聚乙烯醇海绵）。24小时后，两组（一组继续喂食普通鼠粮，另一组开始喂食添加150,000 IU维生素A/kg鼠粮）接受局部肿瘤照射；两组，一组摄取普通鼠粮，另一组摄取补充维生素A的鼠粮，开始进行环磷酰胺治疗；两组，一组摄取普通鼠粮，另一组摄取补充维生素A的鼠粮，既不接受局部肿瘤照射也不接受环磷酰胺治疗。另外两组摄取普通鼠粮，一组既未接种肿瘤也未致伤，另一组未接种肿瘤但致伤，作为对照。伤口断裂强度和海绵修复性胶原蛋白积累（通过羟脯氨酸测量评估）用作伤口愈合的指标。致伤12天后处死小鼠。肿瘤的存在降低了伤口断裂强度和海绵羟脯氨酸含量；补充维生素A在很大程度上抵消了这些影响。局部肿瘤照射减轻了肿瘤对海绵修复性胶原蛋白含量的不利影响，但程度小于补充维生素A。补充维生素A增强了照射对愈合的效果，但照射并未增强维生素A的效果。环磷酰胺，一种全身性类放射抗肿瘤药物，并未改变荷瘤小鼠受损的伤口愈合情况。补充维生素A减轻了环磷酰胺治疗的荷瘤小鼠受损的伤口愈合。补充维生素A还减轻了致伤、肿瘤和肿瘤治疗（局部照射和环磷酰胺）对肾上腺大小增加、白细胞减少、血小板减少和胸腺退化的影响（除了最后一项在环磷酰胺治疗的荷瘤大鼠中未得到减轻）。补充维生素A减轻了未治疗的荷瘤致伤大鼠和接受环磷酰胺治疗大鼠的脾脏肿大。我们假设维生素A的这些抗应激作用部分构成了其减轻荷瘤小鼠受损伤口愈合的作用基础，包括那些接受局部照射或环磷酰胺治疗的小鼠。这些发现对恶性肿瘤患者的护理具有启示意义。
