Zhang Yongfeng, Jin Ben, Miller Haiyan D, Ge Dongxia, Zhang Xin, You Zongbing
Department of Structural & Cellular Biology, Tulane University New Orleans, LA, USA.
Southeast Louisiana Veterans Health Care System New Orleans, LA, USA.
Am J Clin Exp Urol. 2021 Feb 15;9(1):32-43. eCollection 2021.
Lupus is an autoimmune inflammatory disease that affects multiple organs. Cyclin-dependent kinases (CDKs) have been associated with inflammation. The objective of this study was to explore the effects of palbociclib (a CDK4/6 inhibitor) on inflammation in a lupus-prone MRL-lpr mouse model. Twenty mice (10 females and 10 males) were randomized into control group (n=10, treated with vehicle) and treatment group (n=10, treated with 3 cycles of palbociclib at a dose of 120 mg/kg/day for 2 weeks on and 10 weeks off, through oral gavage). Animals were euthanized after the third cycle of treatment. We found that facial skin lesions developed later and smaller in the female mice treated with palbociclib than the female mice in the control group. The lymph node number was less and the lymph node weight was lighter in the female treatment group compared to the female control group. The inflammatory lesions in the kidneys of male mice treated with palbociclib were significantly reduced compared to the male mice in the control group. Our findings suggest that palbociclib treatment reduces inflammation in lupus-prone mice in a gender-specific manner, targeting the facial skin and lymph nodes in the female mice and the kidneys in the male mice.
狼疮是一种影响多个器官的自身免疫性炎症性疾病。细胞周期蛋白依赖性激酶（CDKs）与炎症有关。本研究的目的是探讨帕博西尼（一种CDK4/6抑制剂）对狼疮易感MRL-lpr小鼠模型炎症的影响。将20只小鼠（10只雌性和10只雄性）随机分为对照组（n=10，给予赋形剂）和治疗组（n=10，通过灌胃给予3个周期的帕博西尼，剂量为120mg/kg/天，连续给药2周，停药10周）。在第三个治疗周期后对动物实施安乐死。我们发现，与对照组雌性小鼠相比，接受帕博西尼治疗的雌性小鼠面部皮肤病变出现得更晚且更小。与雌性对照组相比，雌性治疗组的淋巴结数量更少，淋巴结重量更轻。与对照组雄性小鼠相比，接受帕博西尼治疗的雄性小鼠肾脏中的炎症病变明显减少。我们的研究结果表明，帕博西尼治疗以性别特异性方式减轻狼疮易感小鼠的炎症，对雌性小鼠的面部皮肤和淋巴结以及雄性小鼠肾脏产生作用。
