前列宁调控基质金属蛋白酶降解胶原蛋白对前列腺增生治疗的影响  

Effect of Qianliening on Treatment of Prostatic Hyperplasia by Collagen Degradation via Regulating Matrix Metalloproteinase

作　　者：赵锦燕 王雪皎 李斐 林久茂 周建衡[4] ZHAO Jinyan;WANG Xuejiao;LI Fei;LIN Jiumao;ZHOU Jianheng(Fujian Key Laboratory of Integrative Medicine on Geriatrics,Fuzhou 350122,China;Fujian Key Laboratory of Basic Integration of Traditional Chinese and Western Medicine,Fuzhou 350122,China;Institute of Integrative Traditional Chinese and Western Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;College of Integrative Traditional Chinese and Western Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China)

机构地区：[1]福建省中西医结合老年性疾病重点实验室,福州350122 [2]中西医结合基础福建省高等学校重点实验室,福州350122 [3]福建中医药大学中西医结合研究院,福州350122 [4]福建中医药大学中西医结合学院,福州350122

出　　处：《世界中医药》2024年第22期3467-3472,3478,共7页World Chinese Medicine

基　　金：国家自然科学基金面上项目(81173433);福建省自然科学基金项目(2020J01715)。

摘　　要：目的:观察前列宁(QLN)对基质金属蛋白酶-2(MMP-2)及基质金属蛋白酶-2抑制因子(TIMP-2)介导的胶原蛋白Ⅱ、Ⅲ、Ⅳ(CollagenⅡ、Ⅲ、Ⅳ)调控作用,探讨QLN治疗良性前列腺增生(BPH)的作用机制。方法:斯泼累格·多雷(SD)大鼠分空白组、模型组、QLN低剂量、中剂量、高剂量组,模型组、QLN各剂量组BPH造模,观察组QLN灌胃,治疗4周,测量大鼠前列腺重量、体积、计算前列腺指数,免疫组织化学观察CollagenⅡ、Ⅲ、Ⅳ蛋白表达;人前列腺增生细胞(BPH-1)培养,分空白组(对照组即0 mg/mL)、QLN低剂量、中剂量、高剂量组(0.25、0.5、1 mg/mL),倒置显微镜观察细胞形态,细胞计数Kit-8试剂盒(CCK-8)检测细胞活性,蛋白质免疫印迹法检测MMP2、TIMP-2、CollagenⅡ、Ⅲ、Ⅳ蛋白表达。结果:与模型组比较,QLN各剂量组中前列腺重量、体积及指数明显减小(P<0.05),CollagenⅡ、Ⅲ、Ⅳ蛋白表达明显减少(P<0.05);细胞实验显示中、高剂量组BPH-1细胞密度明显减少,生长速度缓慢。CCK-8结果显示,QLN中剂量组、QLN高剂量组24 h及48 h BPH-1细胞活力明显下降(P<0.05),蛋白质免疫印迹显示MMP-2、CollagenⅡ、Ⅲ、Ⅳ蛋白表达明显降低,TIMP-2蛋白表达明显增高,与空白组差异有统计学意义(P<0.05)。结论:QLN可有效降解BPH大鼠前列腺组织中CollagenⅡ、Ⅲ、Ⅳ表达,对BPH-1细胞具有明显抑制作用,其治疗机制可能是QLN介导MMP-2、TIMP-2降解CollagenⅡ、Ⅲ、Ⅳ蛋白达到治疗BPH作用。Objective:To observe the effect of Qianliening(QLN)on collagensⅡ,Ⅲ,andⅣmediated by matrix metalloproteinase-2(MMP-2)and tissue inhibitor of metalloproteinase-2(TIMP-2)and its mechanism in treating benign prostatic hyperplasia(BPH).Methods:Sprague-Dawley(SD)rats were divided into a blank group,model group,low-dose QLN group,medium-dose QLN group,high-dose QLN group,and model group.The BPH model was established in each dose group of QLN,and the treatment group was treated with QLN by gavage.After four weeks of treatment,the weight and volume of the prostate were measured;the prostate index was calculated,and the protein expressions of collagensⅡ,Ⅲ,andⅣwere observed by immunohistochemistry.Human prostatic hyperplasia cells(BPH-1)were cultured and divided into a blank group(control group,0 mg/mL),low-dose QLN group(0.25 mg/mL),medium-dose QLN group(0.5 mg/mL),and high-dose QLN group(1 mg/mL).Cell morphology was observed by an inverted microscope.The cell viability was detected by cell counting Kit-8(CCK-8)assay.The protein expressions of MMP2,TIMP-2,and collagensⅡ,Ⅲ,andⅣwere detected by Western Blot.Results:Compared with the model group,the prostate weight,volume,and index of rats in the QLN groups were significantly reduced(P<0.05),and the protein expression of collagensⅡ,Ⅲ,andⅣwas significantly reduced by(P<0.05).Cell experiment showed that the density of BPH-1 cells in the medium-dose QLN group and high-dose QLN group was significantly reduced,and the cell growth rate was slow.The results of CCK8 showed that the viability of BPH-1 cells in the medium-dose QLN group and high-dose QLN group within 24 hours and 48 hours was significantly reduced(P<0.05).Western Blot showed that the protein expression of MMP-2 and collagensⅡ,Ⅲ,andⅣdecreased significantly,while TIMP-2 protein expression increased significantly.Compared with the blank group,the difference was statistically significant(P<0.05).Conclusion:QLN can effectively degrade the expression of CollagenⅡ,Ⅲ,andⅣin prostate tissue o

关 键 词：前列腺增生 前列宁 细胞外基质 基质金属蛋白酶2 基质金属蛋白酶2抑制因子 胶原蛋白Ⅱ 胶原蛋白Ⅲ 胶原蛋白Ⅳ 

分 类 号：R289.5[医药卫生—方剂学]