摘要
目的通过研究川芎嗪(TMP)对银屑病小鼠皮损内肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-17及血管内皮生长因子(VEGF)表达的影响及其可能的作用机制。方法30只BALB/c小鼠剔除背部约4 cm×2 cm大小区域毛发后随机分为正常组,模型组,低、中、高TMP组,每组6只。正常组涂抹凡士林62.5 mg/d,模型组及TMP各组涂抹5%咪喹莫特乳膏62.5 mg/d,连续7 d;于第4天起,低、中、高TMP组分别予腹腔注射20、40、100 mg/kg盐酸川芎嗪注射液,正常组及模型组注入等量生理盐水,1次/d,连续9 d。观察各组小鼠皮损变化,干预结束后取小鼠背部皮损,实时荧光定量PCR(qRT-PCR)法检测各组皮损中TNF-α、IL-17及VEGF的mRNA表达水平;组织切片HE染色及免疫组织化学染色,观察各组皮损的病理变化及检测TNF-α、IL-17、VEGF蛋白表达量。结果皮损组织病理:模型组小鼠呈现为典型的银屑病样病理改变,TMP组皮损的银屑病样病理表现则较模型组依次减轻。qRT-PCR结果显示:与正常组相比,模型组TNF-α、IL-17、VEGF mRNA相对表达量均升高(P<0.05);与模型组、低TMP组相比,中、高TMP组TNF-αmRNA的表达量下降(P<0.05);与模型组相比,低、中、高剂量TMP组的IL-17 mRNA表达量依次降低(P<0.05);与模型组、低、中TMP组相比,高TMP组VEGF mRNA表达量降低(P<0.05)。免疫组化结果显示:TNF-α、IL-17、VEGF均主要表达于表皮细胞的胞浆内,且与正常组相比,模型组的各蛋白表达量均升高(均P<0.05);与模型组相比,低、中、高TMP组IL-17、VEGF表达量及中TMP组TNF-α表达量降低(均P<0.05);与低TMP组相比,高TMP组TNF-α、IL-17、VEGF表达量及中TMP组IL-17表达量降低(均P<0.05);与中TMP组相比,高TMP组VEGF表达量降低(均P<0.05)。结论川芎嗪可通过降低小鼠银屑病样皮损内的TNF-α、IL-17、VEGF的表达水平,改善小鼠银屑病样皮损的炎症表现。
Objective To investigate the therapeutic effect of tetramethylpyrazine(TMP)on expression levels of tumor necrosis factor-α(TNF-α),interleukin-17(IL-17)and vascular endothelial growth factor(VEGF)in skin lesions of psoriatic mice and its possible mechanism.Methods Thirty BALB/c mice,half male and half female,were randomly divided into the normal group,the model group and the low,medium and high TMP groups after shaving hair in back area of about 2 cm×4 cm,with 6 mice in each group.Mice in the normal group was smeared with vaseline 62.5 mg/d.Mice in the model group and the TMP group were smeared with imiquimod cream 62.5 mg/d for continuous 7 days.From the 4th day,the low,medium and high TMP groups were respectively injected with ligustrazine hydrochloride 20 mg/kg,40 mg/kg and 100 mg/kg,and the normal group and the model group were injected with the same amount of normal saline once a day for 9 consecutive days.Changes of skin lesions were observed in each group.After the intervention,back skin lesions of mice were taken.The expression levels of TNF-α,IL-17 and VEGF mRNA in skin lesions were detected by qRT-PCR.The pathological changes of skin lesions and TNF-α,IL-17 and VEGF protein expression levels in skin lesions of each group were detected by HE staining and immunohistochemical staining.Results Mice in the model group showed typical psoriasis-like pathological changes,while the psoriasis-like pathological changes of skin lesions of the TMP group were successively lighter than those of the model group.Compared with the normal group,the expression levels of TNF-α,IL-17 and VEGF mRNA were significantly higher in the model group(all P<0.05).Compared with the model group and the low TMP group,the expression levels of TNF-αmRNA decreased significantly in the medium TMP group and the high TMP group(P<0.05).Compared with the model group,expression levels of IL-17 mRNA were decreased gradually in the three TMP groups(P<0.05).Compared with the model group,the low TMP group and the medium TMP group,the expression
作者
朱玉婷
晏文
应理晟
王进京
ZHU Yuting;YAN Wen;YING Lisheng;WANG Jinjing(Department of Dermatology,the Affiliated Hospital of Zunyi Medical University,Zunyi 563003,China;Department of Pathology,the Affiliated Hospital of Zunyi Medical University,Zunyi 563003,China)
出处
《天津医药》
CAS
北大核心
2023年第6期590-595,共6页
Tianjin Medical Journal
基金
贵州省自然科学基金项目[黔科合基础-ZK(2023)一般578]
贵州省科技合作计划项目[黔科合LH字(2015)7473号]
遵义市科技计划项目[遵市科合HZ字(2020)217号]。
关键词
银屑病
肿瘤坏死因子α
白细胞介素17
血管内皮生长因子类
川芎嗪
psoriasis
tumor necrosis factor-alpha
interleukin-17
vascular endothelial growth factors
tetramethylpyrazine
