基于非稳态负荷评估衰老及左归丸干预衰老的效果
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1.复旦大学附属华山医院中西医结合研究院;2.上海交通大学药学院药学院

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上海市扬帆计划 (21YF1404000)


Using allostatic load as a tool for evaluating aging and the aging-delaying effects of Zuogui Pill
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1.Institute of Integrated Traditional Chinese and Western Medicine , Huashan Hospital Affiliated to Fudan University;2.Institute of Integrated Traditional Chinese and Western Medicine, Huashan Hospital Affiliated to Fudan University;3.School of Pharmacy, Shanghai Jiao Tong University

Fund Project:

Shanghai Sailing program(21YF1404000)

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    摘要:

    目的 采用非稳态负荷(allostatic load,AL)的理论与方法评估衰老以及左归丸的抗衰老作用。方法 自然衰老大鼠,分别在2、5、8、14、18、21月龄剪尾取血,其中18月龄时随机分为老年对照组、左归丸低剂量组和左归丸高剂量组。左归丸干预3个月后,各组大鼠断颈处死,取用血样以及肌肉、肝脏等组织样本。各月龄、各组大鼠血样用流式细胞术检测T淋巴细胞数量和凋亡率,并检测各血清生化指标,包括低密度脂蛋白胆固醇(low-density lipoprotein cholesterol , LDL-c)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol, HDL-c)、甘油三酯(triglycerides, TG)、总胆固醇(total cholesterol, tCHO)、游离脂肪酸(free fatty acids, FFA)、25羟维生素D(25 hydroxyvitamin D, 25-OH-D)、皮质酮(corticosterone, CORT)、C反应蛋白(c-reactive protein, CRP)、白细胞介素-6(interleukin 6, IL-6)。纳入LDL-c、tCHO、HDL-c、FFA、TG、CORT、IL-6、CRP、25-OH-D、CD3+ T淋巴细胞计数、CD3+ T淋巴细胞凋亡率共11项指标用于AL评分。结果 大鼠血清LDL-c、TG、tCHO、25-OHD、CRP、IL-6随增龄发生显著改变,但变化模式有所不同。CD3+ T淋巴细胞计数随增龄显著降低(P < 0.01),CD3+CD4+CD8+ T淋巴细胞凋亡率随增龄显著升高(P < 0.01)。左归丸干预后,老年大鼠血清CORT水平显著提高(P < 0.01)、CD8+ T淋巴细胞凋亡率显著降低(P < 0.05)。AL评分自5月龄开始升高,至18月龄到达峰值。结论 与单一指标比较,AL能更好表征衰老过程。左归丸可以提高衰老大鼠的应激反应能力,延缓其免疫衰老。

    Abstract:

    Objective Using the concept and method of allostatic load (AL) to evaluate aging and the effectiveness of Zuogui Pill intervention in aging. Methods Natural aging rats were tested at the ages of 2, 5, 8, 14, and 18 months, and were divided into an elderly control group, a low-dose group of Zuogui Pill, and a high-dose group of Zuogui Pill. Intervention with Zuogui Pill for 3 months. Blood samples were taken from the tail of rats of each month and group, and the number of T lymphocytes and apoptosis rate were measured by flow cytometry. Low-density lipoprotein cholesterol (LDL-c), High-density lipoprotein cholesterol (HDL-c), triglycerides (TG), total cholesterol (tCHO), free fatty acids (FFA), 25 hydroxyvitamin D (25-OHD), corticosterone (CORT), C-reactive protein (CRP), Interleukin-6 (IL-6) in rat serum were detected. By identifying the collinearity between indicators and professional considerations, LDL-c, tCHO, HDL-c, FFA, TG, CORT, IL-6, CRP, 25-OHD, CD3+ T cell count, and CD3+ T cell apoptosis rate were included for AL scoring. The threshold for each indicator was established on data from 5-month-old rats, and the score was 1 point below or/and above the threshold. Results The serum LDL-c, TG, tCHO, 25-OHD, CRP, and IL-6 of rats showed significant changes with age, but the change patterns were different. The CD3+ T lymphocyte count significantly decreased with age (P < 0.01), while the apoptosis rates of CD3+, CD4+, and CD8+ T lymphocytes significantly increased with age (P < 0.01). Zuogui Pill can significantly increase the serum CORT level in elderly rats (P < 0.01) and reduce the apoptosis rate of CD8+ T lymphocytes (P < 0.05). The AL score began to increase at 5 months of age and reached its peak at 18 months of age. Conclusion AL can better characterize the aging process compared to a single indicator. Zuogui Pill can improve the stress response ability of aging rats and alleviate their immune aging.

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  • 收稿日期:2023-09-21
  • 最后修改日期:2024-05-28
  • 录用日期:2024-06-10
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