摘要
目的 采用猴免疫缺陷病毒(SIVmac239)感染猕猴艾滋病模型,评价中药益艾康联合抗逆转录病毒治疗(ART)的治疗效果。方法 8只SIVmac239病毒感染的猕猴随机分为两组:ART治疗组、益艾康联合ART治疗组。ART治疗先后分别使用洛匹那韦/利托那韦(LPV/r)和恩曲他滨(FTC)+泰诺福韦(PMPA)+雷特格韦(RAL)进行治疗,检测不同治疗时期猕猴体质量、血常规、血生化、血浆病毒载量以及CD4+T细胞和CD8+T细胞计数及各亚群的变化情况。结果 在LPV/r治疗期,LPV/r单独治疗组的血红蛋白在治疗1、2周时明显降低,随后恢复到治疗前水平(P<0.05),益艾康联合LPV/r治疗组则无显著变化(P>0.05);两组动物的肌酐在治疗期间逐渐升高(P<0.05),组间差异无统计学意义(P>0.05);LPV/r单独治疗组的γ-谷氨酰转肽酶在各时间点均高于益艾康联合LPV/r治疗组,但差异无统计学意义(P>0.05);益艾康联合LPV/r治疗组PD-1^(+)CD_(4)^(+)T细胞百分比治疗后升高(P<0.05),LPV/r单独治疗组无明显变化(P>0.05),益艾康联合LPV/r治疗组PD-1^(+)CD_(4)^(+)T细胞百分比在治疗期间均低于LPV/r单独治疗组,但差异无统计学意义(P>0.05);益艾康联合LPV/r治疗组na6ve CD_(4)^(+)T细胞百分比治疗后降低(P<0.05),LPV/r单独治疗组na6ve CD_(4)^(+)T细胞百分比无明显变化(P>0.05);益艾康联合LPV/r治疗组CD4+Tcm细胞百分比治疗后升高(P<0.05),LPV/r单独治疗组CD_(4)^(+)Tcm细胞百分比无明显变化(P>0.05);使用FTC+PMPA+RAL治疗后,治疗组血浆病毒载量在治疗1周时下降1.80 log10copies/mL,益艾康联合FTC+PMPA+RAL治疗组下降2.40 log10copies/mL,均下降到检测线(1.47 log10copies/mL)以下,停药1周时未见血浆病毒载量反弹,停药2周时益艾康联合FTC+PMPA+RAL治疗组血浆病毒载量出现反弹为2.33 log10copies/mL,FTC+PMPA+RAL治疗组未见反弹,停药3周后两组均出现血浆病毒载量反弹。结论 研究结果表明益艾康联合LPV/r治疗SIVmac239感染猕猴艾滋病模型对体质量及血常规影响较小,可减轻LPV/r造成的肝损伤;可减缓CD_(4)^(+)T细胞计数降低、降低PD-1^(+)CD_(4)^(+)T细胞表达、促进na6ve CD_(4)^(+)T细胞向CD_(4)^(+)Tcm细胞分化调节免疫功能;益艾康联合FTC+PMPA+RAL治疗对感染猴血液常规参数无显著影响,不会对感染猴血浆病毒载量抑制及反弹产生影响。
Objective To evaluate the efficacy of Yiaikang(益艾康)combined with antiretroviral therapy(ART)in the treatment of simian immunodeficiency virus(SIVmac239)infected rhesus monkey AIDS model.Methods Eight SIVmac239 infected macaques were randomly divided into two groups.In the ART treatment group and Yiaikang combined with ART treatment group,lopinavir/ritonavir(LPV/r)and FTC+PMPA+RAL were successively used for ART treatment,and the body weight,blood routine,blood biochemistry,plasma viral load,CD_(4)^(+)T cell and CD_(4)^(+)T cell count,and the changes of each subgroup were detected at different treatment periods.Results Hemoglobin in the LPV/r group decreased significantly after 1-2 weeks of treatment and then returned to the pre-treatment level(P<0.05),there was no significant change in the treatment group of Yiaikang combined with LPV/r(P>0.05).Creatinine in both groups increased gradually during treatment(P<0.05),there was no significant difference between groups(P>0.05).The-glutamyl transpeptidase in LPV/r alone group was higher than that in Yiaikang combined with LPV/r group at all times points,and there was no significant difference(P>0.05).The percentage of PD-1^(+)CD_(4)^(+)Tcells increased after treatment in the Yiaikang combined with LPV/r group(P<0.05),there was no significant change in LPV/r in the treatment group alone(P>0.05),the percentage of PD-1^(+)CD_(4)^(+)T cells in the Yiaikang combined with LPV/r group was lower than that in the LPV/r alone group,but there was no significant dfference(P>0.05).The percentage of naive CD_(4)^(+)T cells decreased after treatment in the Yiaikang combined with LPV/r group(P<0.05),there was no significant change in naive CD_(4)^(+) T cell percentage in LPV/r alone group(P>0.05).The percentage of CD_(4)^(+)Tcm cells increased after treatment in the Yiaikang combined with LPV/r group(P<0.05),there was no significant change in the percentage of CD_(4)^(+)Tcm cells in LPV/r alone group(P>0.05).Plasma viral load in the FTC+PMPA+RAL group decreased by 1.80 logio copies/mL at 1 week of treatment,and in the Yiaikang combined with FTC+PMPA+RAL group decreased by 2.40 logio copies/mL,both of which dropped below the test line(1.47 logio copies/mL).No rebound of plasma viral load was observed at 1 week after drug discontinuation.The rebound of plasma viral load in the Yiaikang combined with FTC+PMPA+RAL group was 2.33 logio copies/mL at 2 weeks after drug discontinuation,but no rebound was observed in the FTC+PMPA+RAL group.Conclusion The results showed that the combination of LPV/r and Yiaikang in SIVmac239 infected rhesus monkey modelhad little effect on body weight and blood routine,and could reduce liver injury caused by LPV/r,and could slow down the decrease of CD_(4)^(+) T cell count.It can reduce the expressions of PD-1^(+)CD_(4)^(+)T cells,promote the dfferentiation of naive CD_(4)^(+)T cells to CD_(4)^(+) Tcm cells and regulate the immune function.Yiaikang combined with FTC+PMPA+RAL had no significant effect on blood routine indexes,and had no effect on viral load inhibition and rebound in plasma of infection monkeys.
作者
赵明亮
王琼
刘本波
丁雪
孟鹏飞
徐立然
庞伟
田仁荣
郑永唐
ZHAO Mingliang;WANG Qiong;LIU Benbo;DING Xue;MENG Pengfei;XU Liran;PANG Wei;TIAN Renrong;ZHENG Yongtang(Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences,Institute of Zoology,Chinese Academy of Sciences,Kunming 650223,Yunnan,China;Faculty of Basic Medicine,Kunming University of Science and Technology,Kunming 650500,Yunnan,China;School of Pharmacy,Dali University,Dali 671000,Yunnan,China;The First Affiliated Hospital of Henan University of Traditional Chinese Medicine,Zhengzhou 450000,Henan,China)
出处
《辽宁中医杂志》
CAS
2023年第3期193-199,共7页
Liaoning Journal of Traditional Chinese Medicine
基金
国家重点研发计划项目(2021YFC2301703)
国家自然科学基金-河南联合基金(U1604287)。
作者简介
赵明亮(1994-),男,甘肃环县人,硕士,研究方向:艾滋病灵长类动物模型;通讯作者:田仁荣(1982-),女,云南华坪人,副研究员,博士,研究方向:HIV靶向病毒储藏库的治疗策略等,E-mail:tianrenrong@mail.kiz.ac.cn;通讯作者:郑永唐(1962-),男,江西赣州人,研究员,博士,研究方向:抗HIV药物体外药效学评价和机制研究等,E-mail:zhengyt@mail.kiz.ac.cn。
