摘要
目的探讨博来霉素诱导硬皮病样改变。方法24只BALB/c小鼠随机分为模型组和对照组,每日分别于背部皮下注射0.1mL博来霉素(300μg/mL)和0.1mL生理盐水,共4周。然后取背部皮肤行组织病理检查及真皮厚度测量,比色法测定羟脯氨酸含量,原位杂交法检测结缔组织生长因子(CTGF)mRNA表达细胞及RT-PCR法测定α1前胶原(pro-COL1A1)和CTGFmRNA表达量。结果模型组小鼠皮肤表现出典型的硬皮病改变,其真皮较对照组显著增厚(P<0.01),羟脯氨酸含量显著升高(P<0.01);CTGFmRNA阳性杂交信号主要分布于真皮成纤维细胞胞浆中,模型组CTGF和pro-COL1A1mRNA表达均较对照组显著增强(P分别<0.05和0.01);模型组皮肤羟脯氨酸含量与pro-COL1A1mRNA表达量呈正相关(P<0.05),而pro-COL1A1mRNA又与CTGFmRNA表达量呈正相关(P<0.01)。结论博来霉素可能通过上调成纤维细胞CTGFmRNA表达而增强pro-COL1A1mRNA表达,最终导致皮肤胶原含量增多。
Objective To investigate the expression of connective tissue growth factor（CTGF） mRNA in the sclerotic skin of mice with bleomycin （BLM）-induced scleroderma. Methods Twenty-four SPF female BALB/c mice were randomly divided into the model group and the control group. The model mice were subcutaneously injected on the back with 0.1 mL of BLM （300 μg/mL, diluted in saline） daily for 4 weeks, while the controls were injected with saline in the same manner. After the final injection the skin section in the injected area was collected for histological examination, measurement of dermis thickness, determination of hydroxyproline contents by a colorimetric method, detection of CTGF mRNA expression by in situ hybridization and measurement of CTGF and pro-collagen αl （pro-COLlAl） mRNA expression by semiquantitative RT-PCR. Results Compared with the control mice, the model mice showed typical scleroderma histologically. The dermis was significantly thicker and the skin hydroxyproline content was significantly higher in the model group than that in the controls （both P 〈 0.01 ）. The positive signals for CTGF mRNA were mainly distributed in the cytoplasm of the fibroblasts in the dermis. The mRNA expression of both CTGF and pro-COLlAl in the model mice was significantly up-regulated （P 〈 0.05, P 〈 0.01, respectively） than that in the controls. The hydroxyproline content in the skin of model mice correlated positively with the expression of pro-COLlAl mRNA （P 〈 0.05）, meanwhile the latter correlated positively with the mRNA expression of CTGF （P 〈 0.01）. Conclusion BLM may increase the expression of pro-COLlAl by up-regulating CTGF mRNA expression, which finally leads to the increase of the collagen content in the skin.
出处
《中华皮肤科杂志》
CAS
CSCD
北大核心
2006年第1期22-25,共4页
Chinese Journal of Dermatology
基金
湖南省科技厅科研基金资助项目(02ssy3080)
