不同皮肤老化小鼠模型的比较
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摘要
目的比较亚急性衰老小鼠模型、光老化小鼠模型与青年小鼠、自然老化小鼠皮肤的异同点。方法分别采用D-半乳糖注射建立亚急性衰老小鼠模型,中波紫外线(ultraviolet B,UVB)照射建立光老化小鼠模型。从皮肤外观、组织学改变、生化指标、基质金属蛋白酶(matrix metalloproteinase,MMP)-1表达等多维度比较亚急性衰老小鼠模型、光老化小鼠模型与青年小鼠及自然老化小鼠的异同。结果亚急性衰老小鼠和自然老化小鼠外观上均表现为皮肤变薄伴细小皱纹,光老化小鼠皮肤明显增厚且皱纹粗大。在皮肤组织学改变方面,自然老化和亚急性衰老小鼠真皮和表皮厚度均降低,胶原纤维和弹力纤维均减少。光老化小鼠表皮和真皮厚度均增加,胶原纤维减少,弹力纤维增多、断裂。光老化小鼠和自然老化小鼠中Ⅲ型胶原比例增加,而亚急性老化小鼠中Ⅲ型胶原无明显变化。与青年小鼠比较,三种老化小鼠中超氧化物歧化酶(superoxide dismutase,SOD)活性、羟脯氨酸(hydroxyproline,Hyp)含量均降低,丙二醛(malondialdehyde,MDA)含量升高,MMP-1表达升高。结论亚急性衰老小鼠模型的皮肤外观和组织学指标接近自然老化小鼠;而光老化小鼠模型与前两者存在明显差异。三者皮肤老化的共同机制可能是ROS介导的MMPs(MMP-1)表达增高,从而导致细胞外基质的降解。本研究为皮肤老化研究中动物模型的选择提供了可靠的实验数据。
Objective To compare the subacute aging mouse model,photoaged mouse model with young adult mouse and naturally-aged mouse.Methods The subacute aging mouse model and photoaged mouse model were established with D-galactose and UVB radiation,respectively.The differences with respect to the appearance,histology,biochemistry and the expression of matrix metalloproteinase(MMP)-1 were compared among these models,young adult mouse and naturally-aged mouse.Results Both subacute aging mice and natural-aged mice presented with thin skin and fine wrinkles,whereas photoaged mice presented with significantly thicker skin and wrinkles.There were reductions of thickness of dermal and epidermis and decreases of the collagen fiber and elastic fiber in both subacute aging mice and naturally-aged mice.However,in photoaged mice,the thickness of epidermis and dermis increased,collagen fibers decreased,whereas elastic fibers increased and fractured.Compared with young adult mice,higher levels of collagen type Ⅲ existed in both naturally-aged mice and photoaged mice,but not in subacute aging mice.The three kinds of aging mice showed reduced activities of superoxide dismutase(SOD) and hydroxyproline(Hyp),but elevated content of malondialdehyde(MDA) and gene and protein expression of MMP-1.Conclusion The appearance,pathological and biochemical changes are similar in subacute aging mice and naturally-aged mice.However,photoaged mice show significant difference with the above two.The common mechanism of skin aging may be the increasing of ROS-mediated MMPs(MMP-1) expression,leading to the degradation of extracellular matrix.This study provides reliable experimental data for the selection of animal models in skin aging studies.
Objective To compare the subacute aging mouse model,photoaged mouse model with young adult mouse and naturally-aged mouse.Methods The subacute aging mouse model and photoaged mouse model were established with D-galactose and UVB radiation,respectively.The differences with respect to the appearance,histology,biochemistry and the expression of matrix metalloproteinase(MMP)-1 were compared among these models,young adult mouse and naturally-aged mouse.Results Both subacute aging mice and natural-aged mice presented with thin skin and fine wrinkles,whereas photoaged mice presented with significantly thicker skin and wrinkles.There were reductions of thickness of dermal and epidermis and decreases of the collagen fiber and elastic fiber in both subacute aging mice and naturally-aged mice.However,in photoaged mice,the thickness of epidermis and dermis increased,collagen fibers decreased,whereas elastic fibers increased and fractured.Compared with young adult mice,higher levels of collagen type Ⅲ existed in both naturally-aged mice and photoaged mice,but not in subacute aging mice.The three kinds of aging mice showed reduced activities of superoxide dismutase(SOD) and hydroxyproline(Hyp),but elevated content of malondialdehyde(MDA) and gene and protein expression of MMP-1.Conclusion The appearance,pathological and biochemical changes are similar in subacute aging mice and naturally-aged mice.However,photoaged mice show significant difference with the above two.The common mechanism of skin aging may be the increasing of ROS-mediated MMPs(MMP-1) expression,leading to the degradation of extracellular matrix.This study provides reliable experimental data for the selection of animal models in skin aging studies.
引文
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[2] 张常娥,魏伟,刘英华,等.D-半乳糖亚急性衰老大鼠模型的建立及评价[J].中国老年学杂志,2012,32(2):742-745.
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[4] 王红丽,吴铁,钱聚标,等.D-半乳糖致衰老模型小鼠皮肤衰老的观察[J].中华老年医学杂志,2004,23(8):566-568.
[5] 李张军,牛新武,肖生祥,等.小鼠皮肤光老化动物模型建立方法的改良[J].西安交通大学学报(医学版),2016,37(1):144-147.
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[8] 石丽君,吴铁,吴志华.D-半乳糖诱导大鼠皮肤衰老的形态学与生化指标观察[J].中华皮肤科杂志,2005,38(3):165-167.
[9] 陈勤,姚媛媛,徐柯乐,等.核桃仁水提物对皮肤老化小鼠皮肤胶原纤维的作用[J].中国老年学杂志,2013,38(21):5383-5385.
[10] 朱彦君,冯光珍,孟宇宏,等.皮肤光老化动物模型的建立[J].中国体视学与图像分析,2004,9(1):51-54.
[11] 纪秀军,闫丙健,赵彩玲.D-半乳糖诱导性亚急性衰老大鼠模型的皮肤胶原代谢及相关通路分子研究[J].中国麻风皮肤病杂志,2016,32(2):77-81.
[12] Oikarnen A.The aging of skin:chronoaging versus photoaing[J].Photodermatol Photoimmunol Photomed,1990,7(1):3-4.
[13] Scharffetter-Kochanek K,Brenneisen P,Wenk J,et al.Photoaging of the skin from phenotype to mechanisms[J].Exp Gerontol,2000,35(3):307-316.
[14] 陶从敏,马文宇.光老化的动物模型研究进展 [J].临床皮肤科杂志,2018,47(6):386-388.
[15] 徐慧,刘健航,陈向东,等.非光暴露皮肤经窄谱中波紫外线照射前后MMP-1的表达[J].中国皮肤性病学杂志,2009,23(1):11-12.
[16] 石潇,陈炜.反复紫外线照射建立皮肤光老化模型[J].中国老年学杂志,2013,33(10):5046-5048.
[2] 张常娥,魏伟,刘英华,等.D-半乳糖亚急性衰老大鼠模型的建立及评价[J].中国老年学杂志,2012,32(2):742-745.
[3] 陈旭,王莹,鞠梅,等.皮肤光老化小鼠模型的构建[J].中国麻风皮肤病杂志,2014,30(3):131-136.
[4] 王红丽,吴铁,钱聚标,等.D-半乳糖致衰老模型小鼠皮肤衰老的观察[J].中华老年医学杂志,2004,23(8):566-568.
[5] 李张军,牛新武,肖生祥,等.小鼠皮肤光老化动物模型建立方法的改良[J].西安交通大学学报(医学版),2016,37(1):144-147.
[6] Miller RA,Nadon NL.Principles of animal use for gerontological research[J].J Gerontol A Biol Sci Med Sci,2000,55(3):B117-123.
[7] Vanhooren V,Libert C.The mouse as a model organism in aging research:usefulness,pitfalls and possibilities[J].Ageing Res Rev,2013,12(1):8-21.
[8] 石丽君,吴铁,吴志华.D-半乳糖诱导大鼠皮肤衰老的形态学与生化指标观察[J].中华皮肤科杂志,2005,38(3):165-167.
[9] 陈勤,姚媛媛,徐柯乐,等.核桃仁水提物对皮肤老化小鼠皮肤胶原纤维的作用[J].中国老年学杂志,2013,38(21):5383-5385.
[10] 朱彦君,冯光珍,孟宇宏,等.皮肤光老化动物模型的建立[J].中国体视学与图像分析,2004,9(1):51-54.
[11] 纪秀军,闫丙健,赵彩玲.D-半乳糖诱导性亚急性衰老大鼠模型的皮肤胶原代谢及相关通路分子研究[J].中国麻风皮肤病杂志,2016,32(2):77-81.
[12] Oikarnen A.The aging of skin:chronoaging versus photoaing[J].Photodermatol Photoimmunol Photomed,1990,7(1):3-4.
[13] Scharffetter-Kochanek K,Brenneisen P,Wenk J,et al.Photoaging of the skin from phenotype to mechanisms[J].Exp Gerontol,2000,35(3):307-316.
[14] 陶从敏,马文宇.光老化的动物模型研究进展 [J].临床皮肤科杂志,2018,47(6):386-388.
[15] 徐慧,刘健航,陈向东,等.非光暴露皮肤经窄谱中波紫外线照射前后MMP-1的表达[J].中国皮肤性病学杂志,2009,23(1):11-12.
[16] 石潇,陈炜.反复紫外线照射建立皮肤光老化模型[J].中国老年学杂志,2013,33(10):5046-5048.