刺山柑总生物碱对系统性硬皮病模型小鼠Notch通路的影响  

Effects of Capparis spinosa Total Alkaloid on Notch Pathway in Mice with Systemic Sclerosis

作　　者：李伟[1] 卢军[1] 阿依提拉·麦麦提江 康小龙[1] LI Wei;LU Jun;Ayitila·Maimaitijiang;KANG Xiaolong(Dept.of Pharmacy,TCM Hospital of Affiliated to Xinjiang Medical University,Urumqi 830000,China)

机构地区：[1]新疆医科大学附属中医医院药学部

出　　处：《中国药房》2019年第23期3205-3209,共5页China Pharmacy

基　　金：国家自然科学基金资助项目（No.81760560）

摘　　要：目的:研究刺山柑总生物碱对系统性硬皮病(SSc)模型小鼠Notch通路相关蛋白Notch2、Delta-like 3(DLL3)、Jagged1和Notch胞内段1(NICD1)的影响。方法:将BALB/c小鼠随机分为空白对照组、模型组、阳性对照组(青霉胺125 mg/kg)和刺山柑总生物碱低、中、高剂量组(225、450、900 mg/kg),每组16只。除空白对照组外,其余各组小鼠皮下注射博来霉素4周复制SSc模型,刺山柑总生物碱各剂量组小鼠外敷相应剂量的刺山柑总生物碱乳膏,阳性对照组小鼠灌胃相应剂量的青霉胺,空白对照组和模型组小鼠外敷不含药的乳膏基质,每天1次,连续给药8周。末次给药后4 h,取各组小鼠给药区皮肤,采用实时荧光定量聚合酶链式反应(q PCR)法检测皮肤组织中Notch2、NICD1 mRNA表达,酶联免疫吸附法测定皮肤组织中DLL3含量,免疫组化法检测皮肤组织中Jagged1蛋白表达。结果:与空白对照组比较,模型组小鼠皮肤组织中Notch2、NICD1 mRNA及DLL3含量、Jagged1蛋白表达均显著升高,差异均有统计学意义(P<0.01)。与模型组比较,刺山柑总生物碱中、高剂量组和阳性对照组小鼠皮肤组织中NICD1 mRNA、DLL3含量、Jagged1蛋白表达均显著降低,刺山柑总生物碱高剂量组和阳性对照组小鼠皮肤组织中Notch2 mRNA表达显著降低,差异均有统计学意义(P<0.05或P<0.01)。结论:刺山柑总生物碱可抑制SSc模型小鼠皮肤组织中Notch2、NICD1、DLL3及Jagged1的异常表达,对SSc模型小鼠Notch通路的过度激活有一定的抑制作用。OBJECTIVE:To study the effects of Capparis spinosa total alkaloid on Notch pathways related protein Notch2,Delta-like 3(DLL3),Jagged1 and Notch intracellular domain 1(NICD1)in mice with systemic sclerosis(SSc).METHODS:BALB/c mice were randomly divided into blank control group,model group,positive control group(penicillamine 125 mg/kg),C.spinosa total alkaloid low-dose,medium-dose and high-dose groups(225,450,900 mg/kg),with 16 mice in each group.Except for blank control group,other groups were given bleomycin subcutaneously for 4 weeks to induce SSc model.C.spinosa total alkaloid groups were given relevant dose of C.spinosa total alkaloid cream for external use.Positive control group was given relevant dose of penicillamine intragastrically.Blank control group and model groups were given cream matrix without drug,once a day,for consecutive 8 weeks.4 h after last administration,the skin of the administration area of each group of mice was collected.mRNA expression of Notch2 and NICD1 was detected by real-time PCR;the content of DLL3 was measured by ELISA;the protein expression of Jagged1 in skin tissue was detected by immunohistochemstry.RESULTS:Compared with blank control group,mRNA expression of Notch2 and NICD1,DLL3 content,protein expression of Jagged1 were markedly increased,with statistical significance(P<0.01).Compared with model group,mRNA expression of NICD1,DLL3 content and protein expression of Jagged1 were decreased significantly in C.spinosa total alkaloid medium-dose and high-dose groups,positive control group,mRNA expression of Notch2 in skin tissue were decreased significantly in C.spinosa total alkaloid high-dose group and positive control group,with statistical significance(P<0.05 or P<0.01).CONCLUSIONS:C.spinosa total alkaloid can inhibit the abnormal expression of Notch2,NICD1,DLL3 and Jagged1 in skin tissue of SSc model mice,and inhibit over activation of Notch pathway in SSc model mice.

关 键 词：刺山柑总生物碱 系统性硬皮病 NOTCH2 Notch胞内段1 Delta-like 3 JAGGED1 小鼠 

分 类 号：R965.1[医药卫生—药理学]