目的探究参七虫草胶囊治疗肺纤维化的机制。方法将80只雄性SD大鼠随机分成空白组、模型组、泼尼松组、参七虫草胶囊组,每组20只。采用博莱霉素气管内滴注法复制肺纤维化模型。给药后15、30d,分别观察各组大鼠肺组织病理变化,并采用免疫...目的探究参七虫草胶囊治疗肺纤维化的机制。方法将80只雄性SD大鼠随机分成空白组、模型组、泼尼松组、参七虫草胶囊组,每组20只。采用博莱霉素气管内滴注法复制肺纤维化模型。给药后15、30d,分别观察各组大鼠肺组织病理变化,并采用免疫组织化学方法检测肺组织中基质金属蛋白酶-9(matrix metalloproteinases-9,MMP-9)和基质金属蛋白酶抑制剂-1(issue inhibitor of metalloproteinase-1,TIMP-1)的表达水平。结果与模型组比较,参七虫草胶囊组、泼尼松组大鼠各时点肺泡炎性反应和肺纤维化程度明显减轻,各时点泼尼松组、参七虫草胶囊组肺组织MMP-9、TIMP-1表达水平显著降低(P<0.05,或P<0.01)。结论参七虫草胶囊抑制肺纤维化早期肺泡的炎性反应与其降低肺组织MMP-9、TIMP-1表达水平有关。展开更多
本研究旨在检测弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)中基质金属蛋白酶-26(MMP-26)、金属蛋白酶组织抑制蛋白-4(TIMP-4)及基质金属蛋白酶-9(MMP-9)的表达,探讨其与DLBCL发生及进展的关系。采用免疫组织化学SABC法检...本研究旨在检测弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)中基质金属蛋白酶-26(MMP-26)、金属蛋白酶组织抑制蛋白-4(TIMP-4)及基质金属蛋白酶-9(MMP-9)的表达,探讨其与DLBCL发生及进展的关系。采用免疫组织化学SABC法检测了95例DLBCL患者淋巴瘤组织中MMP-26、TIMP-4和MMP-9的表达,并分析它们与DLBCL临床病理指标的关系。结果表明,与淋巴结反应性增生(20例)相比较,不同类型的DLBCL高表达MMP-26、TIMP-4、MMP-9。MMP-26表达阳性率与免疫分型有关(P<0.05),生发中心型(GCB)中MMP-26的表达低于non-GCB中MMP-26表达,而与临床分期、年龄、性别、疾病部位无关(P>0.05);MMP-9表达阳性率与临床分期有关,Ⅲ期、Ⅳ期患者MMP-9蛋白的表达阳性率明显高于Ⅰ、Ⅱ期患者(P<0.05),而与免疫分型、年龄、性别、结外病变无关(P>0.05);TIMP-4的表达与免疫分型、临床分期、年龄、性别、结外病变均无相关性关(P>0.05)。DLBCL病理组织中MMP-26与TIMP-4表达无相关性,与MMP-9蛋白的表达呈正相关(r=0.486,P<0.05)。结论:MMP-26、MMP-9协同表达于DLBCL,MMP-26可能参与DLBCL的发展及侵袭性,MMP-26的表达与DLBCL病理亚型有关,MMP-26可能作为DLBCL分型的参考指标,并有助于对DLBCL恶性程度及预后的预测,其本身有可能成为一个潜在的治疗靶点。展开更多
Background: Previous research suggested that insulin-like growth factor binding protein related protein 1(IGFBPrP1), as a novel mediator, contributes to hepatic fibrogenesis. Matrix metalloproteinases(MMP) and tissue ...Background: Previous research suggested that insulin-like growth factor binding protein related protein 1(IGFBPrP1), as a novel mediator, contributes to hepatic fibrogenesis. Matrix metalloproteinases(MMP) and tissue inhibitors of metalloproteinases(TIMP) play an essential role in hepatic fibrogenesis by regulating homeostasis and remodeling of the extracellular matrix(ECM). However, the interaction between IGFBPrP1 and MMP/TIMP is not clear. The present study was to knockdown IGFBPrP1 to investigate the correlation between IGFBPrP1 and MMP/TIMP in hepatic fibrosis. Methods: Hepatic fibrosis was induced by thioacetamide(TAA) in mice. Knockdown of IGFBPrP1 expression by ultrasound-targeted microbubble destruction-mediated CMB-shRNA-IGFBPrP1 delivery, or inhibition of the Hedgehog(Hh) pathway by cyclopamine treatment, was performed in TAA-induced liver fibrosis mice. Hepatic fibrosis was determined by hematoxylin and eosin and Sirius red staining. Hepatic expression of IGFBPrP1, α-smooth muscle actin( α-SMA), transforming growth factor β 1(TGF β1), collagen I, MMPs/TIMPs, Sonic Hedgehog(Shh), and glioblastoma family transcription factors(Gli1) were investigated by immunohistochemical staining and Western blotting analysis. Results: We found that hepatic expression of IGFBPrP1, TGF β1, α-SMA, and collagen I were increased longitudinally in mice with TAA-induced hepatic fibrosis, concomitant with MMP2/TIMP2 and MMP9/TIMP1 imbalance and Hh pathway activation. Knockdown of IGFBPrP1 expression, or inhibition of the Hh pathway, reduced the hepatic expression of IGFBPrP1, TGF β1, α-SMA, and collagen I and re-established MMP2/TIMP2 and MMP9/TIMP1 balance. Conclusions: Our findings suggest that IGFBPrP1 knockdown attenuates liver fibrosis by re-establishing MMP2/TIMP2 and MMP9/TIMP1 balance, concomitant with the inhibition of hepatic stellate cell activation, down-regulation of TGF β1 expression, and degradation of the ECM. Furthermore, the Hh pathway mediates IGFBPrP1 knockdown-induced attenuation of hepatic fibro展开更多
文摘目的探究参七虫草胶囊治疗肺纤维化的机制。方法将80只雄性SD大鼠随机分成空白组、模型组、泼尼松组、参七虫草胶囊组,每组20只。采用博莱霉素气管内滴注法复制肺纤维化模型。给药后15、30d,分别观察各组大鼠肺组织病理变化,并采用免疫组织化学方法检测肺组织中基质金属蛋白酶-9(matrix metalloproteinases-9,MMP-9)和基质金属蛋白酶抑制剂-1(issue inhibitor of metalloproteinase-1,TIMP-1)的表达水平。结果与模型组比较,参七虫草胶囊组、泼尼松组大鼠各时点肺泡炎性反应和肺纤维化程度明显减轻,各时点泼尼松组、参七虫草胶囊组肺组织MMP-9、TIMP-1表达水平显著降低(P<0.05,或P<0.01)。结论参七虫草胶囊抑制肺纤维化早期肺泡的炎性反应与其降低肺组织MMP-9、TIMP-1表达水平有关。
文摘本研究旨在检测弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)中基质金属蛋白酶-26(MMP-26)、金属蛋白酶组织抑制蛋白-4(TIMP-4)及基质金属蛋白酶-9(MMP-9)的表达,探讨其与DLBCL发生及进展的关系。采用免疫组织化学SABC法检测了95例DLBCL患者淋巴瘤组织中MMP-26、TIMP-4和MMP-9的表达,并分析它们与DLBCL临床病理指标的关系。结果表明,与淋巴结反应性增生(20例)相比较,不同类型的DLBCL高表达MMP-26、TIMP-4、MMP-9。MMP-26表达阳性率与免疫分型有关(P<0.05),生发中心型(GCB)中MMP-26的表达低于non-GCB中MMP-26表达,而与临床分期、年龄、性别、疾病部位无关(P>0.05);MMP-9表达阳性率与临床分期有关,Ⅲ期、Ⅳ期患者MMP-9蛋白的表达阳性率明显高于Ⅰ、Ⅱ期患者(P<0.05),而与免疫分型、年龄、性别、结外病变无关(P>0.05);TIMP-4的表达与免疫分型、临床分期、年龄、性别、结外病变均无相关性关(P>0.05)。DLBCL病理组织中MMP-26与TIMP-4表达无相关性,与MMP-9蛋白的表达呈正相关(r=0.486,P<0.05)。结论:MMP-26、MMP-9协同表达于DLBCL,MMP-26可能参与DLBCL的发展及侵袭性,MMP-26的表达与DLBCL病理亚型有关,MMP-26可能作为DLBCL分型的参考指标,并有助于对DLBCL恶性程度及预后的预测,其本身有可能成为一个潜在的治疗靶点。
基金supported by grants from National Natural Science Foundation of China(81670559)Key Research and Development Project of Shanxi Province(201603D421023)+2 种基金Youth Fund of Shanxi Medical University(02201514)Graduate Student Education Innovation Project of Shanxi(2016BY077)Youth Fund of Ap-plied Basic Research Program of Shanxi(201701D221175)
文摘Background: Previous research suggested that insulin-like growth factor binding protein related protein 1(IGFBPrP1), as a novel mediator, contributes to hepatic fibrogenesis. Matrix metalloproteinases(MMP) and tissue inhibitors of metalloproteinases(TIMP) play an essential role in hepatic fibrogenesis by regulating homeostasis and remodeling of the extracellular matrix(ECM). However, the interaction between IGFBPrP1 and MMP/TIMP is not clear. The present study was to knockdown IGFBPrP1 to investigate the correlation between IGFBPrP1 and MMP/TIMP in hepatic fibrosis. Methods: Hepatic fibrosis was induced by thioacetamide(TAA) in mice. Knockdown of IGFBPrP1 expression by ultrasound-targeted microbubble destruction-mediated CMB-shRNA-IGFBPrP1 delivery, or inhibition of the Hedgehog(Hh) pathway by cyclopamine treatment, was performed in TAA-induced liver fibrosis mice. Hepatic fibrosis was determined by hematoxylin and eosin and Sirius red staining. Hepatic expression of IGFBPrP1, α-smooth muscle actin( α-SMA), transforming growth factor β 1(TGF β1), collagen I, MMPs/TIMPs, Sonic Hedgehog(Shh), and glioblastoma family transcription factors(Gli1) were investigated by immunohistochemical staining and Western blotting analysis. Results: We found that hepatic expression of IGFBPrP1, TGF β1, α-SMA, and collagen I were increased longitudinally in mice with TAA-induced hepatic fibrosis, concomitant with MMP2/TIMP2 and MMP9/TIMP1 imbalance and Hh pathway activation. Knockdown of IGFBPrP1 expression, or inhibition of the Hh pathway, reduced the hepatic expression of IGFBPrP1, TGF β1, α-SMA, and collagen I and re-established MMP2/TIMP2 and MMP9/TIMP1 balance. Conclusions: Our findings suggest that IGFBPrP1 knockdown attenuates liver fibrosis by re-establishing MMP2/TIMP2 and MMP9/TIMP1 balance, concomitant with the inhibition of hepatic stellate cell activation, down-regulation of TGF β1 expression, and degradation of the ECM. Furthermore, the Hh pathway mediates IGFBPrP1 knockdown-induced attenuation of hepatic fibro
