Rasik A M, Shukla A
Pharmacology Division, Central Drug Research Institute, Lucknow, India.
Int J Exp Pathol. 2000 Aug;81(4):257-63. doi: 10.1046/j.1365-2613.2000.00158.x.
This investigation studied the contribution of antioxidants in delaying healing in excision cutaneous wounds (8 mm) in diabetic, aged and immunocompromised animals. Skin levels of catalase, glutathione (GSH), ascorbic acid (AA) and vitamin E in streptozotocin-induced diabetic rat were lower as compared to nondiabetics. The 7-d wound tissue of diabetic rats showed an increased vitamin E level along with depleted GSH content. In aged rats (18 months old), higher levels of skin superoxide dismutase (SOD), glutathione peroxidase (Gpx) and thiobarbituric acid reactive substances (TBARS) and lower levels of catalase and GSH were found as compared to their values in young rats (3-4 months old). The levels of SOD, GPx, catalase, AA, GSH and vitamin E in 7-d wound tissue of aged rats were significantly lower in comparison to those in young rats. However, TBARS were elevated in these wound tissues. The non-wounded skin of immunocompromised (athymic) mice showed lower levels of SOD, catalase, and TBARS and higher GSH and GPx levels in comparison to those present in normal mouse skin. Surprisingly, the analysis of 7-d wound tissue showed higher levels of SOD, catalase, GPx, and GSH and lower TBARS level in athymic mice compared to the wound tissue of normal mice. Thus low levels of antioxidants accompanied by raised levels of markers of free radical damage play a significant role in delaying wound healing in aged rats. In diabetic rats reduced glutathione levels may have a contributory role in delaying the healing process. However, in immunocompromised mice the antioxidant status following injury showed an adapted response.
本研究探讨了抗氧化剂对糖尿病、老龄和免疫功能低下动物切除性皮肤伤口(8毫米)愈合延迟的影响。与非糖尿病大鼠相比,链脲佐菌素诱导的糖尿病大鼠皮肤中的过氧化氢酶、谷胱甘肽(GSH)、抗坏血酸(AA)和维生素E水平较低。糖尿病大鼠7天的伤口组织中维生素E水平升高,同时GSH含量减少。与年轻大鼠(3 - 4个月大)相比,老龄大鼠(18个月大)皮肤中的超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(Gpx)和硫代巴比妥酸反应性物质(TBARS)水平较高,而过氧化氢酶和GSH水平较低。老龄大鼠7天伤口组织中的SOD、GPx、过氧化氢酶、AA、GSH和维生素E水平与年轻大鼠相比显著降低。然而,这些伤口组织中的TBARS升高。与正常小鼠皮肤相比,免疫功能低下(无胸腺)小鼠的未受伤皮肤中SOD、过氧化氢酶和TBARS水平较低,而GSH和GPx水平较高。令人惊讶的是,对7天伤口组织的分析显示,与正常小鼠的伤口组织相比,无胸腺小鼠中SOD、过氧化氢酶、GPx和GSH水平较高,而TBARS水平较低。因此,抗氧化剂水平低且自由基损伤标志物水平升高在老龄大鼠伤口愈合延迟中起重要作用。在糖尿病大鼠中,还原型谷胱甘肽水平降低可能在延迟愈合过程中起作用。然而,在免疫功能低下的小鼠中,受伤后的抗氧化状态表现出适应性反应。