脂肪干细胞抑制UVB诱导的细胞外基质降解的机制研究  

The Mechanism of Adipose Derived Stem Cells Inhibiting UVB-induced Extracellular Matrix Degradation

作　　者：马旭[1] 杨大平[1] 刘国锋[1] 公美华 李宁[1] 李春阳[1] 张攀[1] MA Xu;YANG Da-ping;LIU Guo-feng;GONG Mei-hua;LI Ning;LI Chun-yang;ZHANG Pan(Department of Plastic Surgery,the Second Affiliated Hospital of Harbin Medical University,Harbin 150086,Heilongjiang,China)

机构地区：[1]哈尔滨医科大学附属第二医院整形美容科

出　　处：《中国美容医学》2019年第6期67-72,共6页Chinese Journal of Aesthetic Medicine

基　　金：哈尔滨医科大学创新科学研究资助项目(编号:2017LCZX49);国家自然科学基金(编号:81771994)

摘　　要：目的:细胞微环境在调控细胞定位、细胞行为和细胞分化等方面发挥重要作用。细胞外基质(Etracellular matrix,ECM)在塑造干细胞微环境中起着最关键的作用,与上皮干细胞接触,调节干细胞命运,其中整合素和胶原蛋白在干细胞的调节和维持中发挥重要作用。本研究中,笔者假设UVB照射通过改变ECM诱导皮肤光老化,并且应用脂肪干细胞(Adipose derived stem cells,ADSCs)可以逆转光老化。方法:将C57BL/6J小鼠作为研究对象,分为对照组、UVB组和UVB+ADSCs组。采用HE和Masson染色鉴定各组的组织学差异,应用免疫荧光分析和RT-PCR技术检测三组间ECM组分表达的差异性。评估整合素α2(Integrinα2),增殖细胞核抗原(Proliferating cell nuclear antigen,PCNA),抗凋亡蛋白Bcl-2在各组的表达情况。结果:HE和Masson染色结果显示UVB照射明显增加表皮厚度,应用ADSCs后表皮厚度与对照组接近。UVB组整合素α2、胶原蛋白Ⅲ和抗凋亡蛋白Bcl-2的表达水平均低于对照组,而UVB+ADSCs组各因子表达高于UVB组,与对照组接近(P<0.05)。基质金属蛋白酶2(Matrix metalloproteinase 2,MMP 2)、基质金属蛋白酶9(Matrix metalloproteinase 9,MMP 9)和PCNA的表达趋势与上述相反。结论:笔者发现UVB照射通过改变ECM而导致典型的光老化征象,并且UVB抑制抗凋亡蛋白Bcl-2的表达和整合素α2的表达。Bcl-2和整合素α2有望成为抑制光老化的作用因子。Objective The stem cell microenvironment plays an essential role in regulating cell localization, cell behavior and cell differentiation. Extracellular matrix(ECM) plays a key role in shaping the stem cell microenvironment, and ECM contacts with epithelial stem cells which regulates the fate of stem cells. And integrins and collagens play an important role in stem cell regulation and maintenance of stemness. In our study, we hypothesized that UVB irradiation induces skin photoaging by altering ECM, and the transplantation of adipose stem cells(ADSCs) can reverse photoaging. Methods C57BL/6J mice were used to establish photoaging model, and were divided into control group, UVB group and UVB+ADSCs group. The histological differences of each group were identified by HE and Masson staining. The differences of ECM components expression among the three groups were detected by immunofluorescence analysis and RT-PCR. And the expression of integrin α2, proliferating cell nuclear antigen(PCNA) and anti-apoptotic protein Bcl-2 were also evaluated. Results HE and Masson staining showed that UVB irradiation significantly increased the thickness of the epidermis, and after ADSCs transplanted, the thickness of the epidermis was similar to that of the control group. The expression levels of Integrin α2, collagen Ⅲ and Bcl-2 in the UVB group were lower than those in the control group, while the expression of each factor in the UVB+ADSCs group was close to the control group(P<0.05).The expression trends of MMP 2, MMP 9 and PCNA are opposite to those described above. Conclusion We found that UVB irradiation leads to typical signs of photoaging by altering ECM, and UVB inhibits the expression of the anti-apoptotic protein Bcl-2 and Integrin α2. Bcl-2 and Integrin α2 are expected to act as inhibitors of photoaging.

关 键 词：光老化 UVB 脂肪干细胞 细胞外基质 Bcl-2 整合素Α2 

分 类 号：R329.28[医药卫生—人体解剖和组织胚胎学]