目的 基于巨噬细胞自噬探讨参芩龙清肺培元颗粒的作用机制。方法 选择人类免疫缺陷病毒(HIV)/艾滋病(AIDS)合并肺部感染痰热壅肺证患者36例,应用流式细胞术检测治疗前后患者外周血T淋巴细胞亚群中CD4^(+)及CD8^(+)T淋巴细胞计数,巨噬细...目的 基于巨噬细胞自噬探讨参芩龙清肺培元颗粒的作用机制。方法 选择人类免疫缺陷病毒(HIV)/艾滋病(AIDS)合并肺部感染痰热壅肺证患者36例,应用流式细胞术检测治疗前后患者外周血T淋巴细胞亚群中CD4^(+)及CD8^(+)T淋巴细胞计数,巨噬细胞亚群CD11b、CD86、CD206的表达及巨噬细胞自噬探针CD11b+DALGreen、CD86+DALGreen、CD206+DALGreen的表达。ELISA法检测治疗前后血清肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、IL-10、转化生长因子(TGF)-β1等炎性因子的表达。采用荧光定量PCR法检测治疗前后患者外周血中组蛋白去乙酰化酶(HDAC)2 m RNA、Unc-51样激酶1(ULK1)m RNA的表达。结果 治疗后,患者CD11b、CD206、CD11b+DALGreen、CD206+DALGreen、ULK1 m RNA表达明显升高(P<0.05);CD86、TNF-α、IL-1β、HDAC2 m RNA的表达明显下降(P<0.05);CD4^(+)T淋巴细胞计数、IL-10、TGF-β1表达呈上升趋势(P>0.05)。结论 参芩龙清肺培元颗粒可能通过调节HDAC2/ULK1信号轴,促进巨噬细胞自噬,调节M1/M2的平衡,抑制炎症反应,从而发挥治疗HIV/AIDS患者合并肺部感染的作用。展开更多
Debate regarding the premature aging of knee joints in acquired immune deficiency syndrome(AIDS)patients has remained contentious,with conjectures pointing towards its correlation with distinct antiviral regimes.Prote...Debate regarding the premature aging of knee joints in acquired immune deficiency syndrome(AIDS)patients has remained contentious,with conjectures pointing towards its correlation with distinct antiviral regimes.Protease inhibitors(PIs)stand as a prominent class of antiviral agents frequently utilized in AIDS management and have been significantly linked to premature senescence.This study aimed to investigate whether PI-containing regimens would accelerate osteoarthritis(OA)development and explore the molecular mechanisms underlying this association.A retrospective cohort of 151 HIV-infected individuals,categorized into PI and non-PI groups,was established.Patients in PI group exhibited lower KOOS and a higher prevalence of radiological knee OA than those in non-PI group.Additionally,25 anti-HIV drugs were screened and among all antiviral drugs,lopinavir had the most detrimental impact on cartilage anabolism,accelerating cartilage senescence and promoting mouse OA development.Mechanistically,lopinavir accelerated cellular senescence by inhibiting Zmpste24 and interfering nuclear membrane stability,which leads to decreased binding between nuclear membrane-binding protein Usp7 and Mdm2 and activates Usp7/Mdm2/p53 pathway.Zmpste24 overexpression reduces OA severity in mice.These findings suggest that PI-containing regimens accelerate cartilage senescence and OA development through Zmpste24 inhibition,which provides new insights into the selection of HIV regimens.展开更多
文摘目的 基于巨噬细胞自噬探讨参芩龙清肺培元颗粒的作用机制。方法 选择人类免疫缺陷病毒(HIV)/艾滋病(AIDS)合并肺部感染痰热壅肺证患者36例,应用流式细胞术检测治疗前后患者外周血T淋巴细胞亚群中CD4^(+)及CD8^(+)T淋巴细胞计数,巨噬细胞亚群CD11b、CD86、CD206的表达及巨噬细胞自噬探针CD11b+DALGreen、CD86+DALGreen、CD206+DALGreen的表达。ELISA法检测治疗前后血清肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、IL-10、转化生长因子(TGF)-β1等炎性因子的表达。采用荧光定量PCR法检测治疗前后患者外周血中组蛋白去乙酰化酶(HDAC)2 m RNA、Unc-51样激酶1(ULK1)m RNA的表达。结果 治疗后,患者CD11b、CD206、CD11b+DALGreen、CD206+DALGreen、ULK1 m RNA表达明显升高(P<0.05);CD86、TNF-α、IL-1β、HDAC2 m RNA的表达明显下降(P<0.05);CD4^(+)T淋巴细胞计数、IL-10、TGF-β1表达呈上升趋势(P>0.05)。结论 参芩龙清肺培元颗粒可能通过调节HDAC2/ULK1信号轴,促进巨噬细胞自噬,调节M1/M2的平衡,抑制炎症反应,从而发挥治疗HIV/AIDS患者合并肺部感染的作用。
基金supported by Natural Science Foundation of China(82472476)Fundamental Research Funds for the Central Universities(YG2023ZD15)+2 种基金The Youth Talent Program from Shanghai Health System(2022YQ020)AI-Driven Reform of Research Paradigms Empowers Discipline Advancement Initiatives from Shanghai Municipal Education Commission(Grant No.JWAIZD-7)the Natural Science Foundation of Shanghai(23ZR1437300).
文摘Debate regarding the premature aging of knee joints in acquired immune deficiency syndrome(AIDS)patients has remained contentious,with conjectures pointing towards its correlation with distinct antiviral regimes.Protease inhibitors(PIs)stand as a prominent class of antiviral agents frequently utilized in AIDS management and have been significantly linked to premature senescence.This study aimed to investigate whether PI-containing regimens would accelerate osteoarthritis(OA)development and explore the molecular mechanisms underlying this association.A retrospective cohort of 151 HIV-infected individuals,categorized into PI and non-PI groups,was established.Patients in PI group exhibited lower KOOS and a higher prevalence of radiological knee OA than those in non-PI group.Additionally,25 anti-HIV drugs were screened and among all antiviral drugs,lopinavir had the most detrimental impact on cartilage anabolism,accelerating cartilage senescence and promoting mouse OA development.Mechanistically,lopinavir accelerated cellular senescence by inhibiting Zmpste24 and interfering nuclear membrane stability,which leads to decreased binding between nuclear membrane-binding protein Usp7 and Mdm2 and activates Usp7/Mdm2/p53 pathway.Zmpste24 overexpression reduces OA severity in mice.These findings suggest that PI-containing regimens accelerate cartilage senescence and OA development through Zmpste24 inhibition,which provides new insights into the selection of HIV regimens.
