Cherry Catherine L, Lal Luxshimi, Thompson Katherine A, McLean Catriona A, Ross Lisa L, Hernandez Jaime, Wesselingh Steven L, McComsey Grace
Burnet Institute, Melbourne, Victoria, Australia.
J Acquir Immune Defic Syndr. 2005 Mar 1;38(3):263-7.
Lipoatrophy is an important manifestation of the lipodystrophy syndrome and is particularly associated with stavudine exposure. Increased apoptosis has been suggested as a possible mechanism of lipoatrophy. We assessed the degree and reversibility of adipocyte apoptosis in patients with lipoatrophy before and 48 weeks after substituting abacavir or zidovudine for stavudine.
Apoptotic adipocytes were identified using terminal transferase dUTP nick end labeling and quantified using video image analysis.
Fat biopsy specimens were obtained from patients before (n = 15) and 48 weeks after (n = 10) switching from stavudine and from 20 HIV-uninfected controls. More apoptotic cells were seen in fat samples from patients with lipoatrophy treated with stavudine than in specimens from controls (P < 0.0001). Forty-eight weeks after switching from stavudine to abacavir or zidovudine, there was a reduction in apoptotic cells per unit area (P = 0.01) and as a proportion of all adipocytes present (P = 0.02) in patient biopsy specimens. Levels of adipocyte apoptosis in the 48-week biopsy specimens were no longer significantly different from those seen in control biopsy specimens (P > 0.1).
Increased apoptosis is present in fat samples from patients with lipoatrophy treated with stavudine. This improves toward normal within 48 weeks of switching from stavudine to abacavir or zidovudine, suggesting a causative role for stavudine in this process.
脂肪萎缩是脂肪代谢障碍综合征的重要表现，尤其与司他夫定的使用有关。细胞凋亡增加被认为是脂肪萎缩的一种可能机制。我们评估了在将阿巴卡韦或齐多夫定替代司他夫定之前及之后48周，脂肪萎缩患者脂肪细胞凋亡的程度及可逆性。
使用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法鉴定凋亡脂肪细胞，并通过视频图像分析进行定量。
从正在使用司他夫定的脂肪萎缩患者（n = 15）、改用司他夫定48周后的患者（n = 10）以及20名未感染HIV的对照者身上获取脂肪活检标本。使用司他夫定治疗的脂肪萎缩患者的脂肪样本中可见的凋亡细胞比对照组标本中的更多（P < 0.0001）。从司他夫定换用阿巴卡韦或齐多夫定48周后，患者活检标本中每单位面积的凋亡细胞数量减少（P = 0.01），且占所有脂肪细胞的比例也减少（P = 0.02）。48周活检标本中的脂肪细胞凋亡水平与对照活检标本中的不再有显著差异（P > 0.1）。
使用司他夫定治疗的脂肪萎缩患者的脂肪样本中存在细胞凋亡增加的情况。从司他夫定换用阿巴卡韦或齐多夫定后48周内，这种情况向正常水平改善，提示司他夫定在此过程中起致病作用。
