目的 酶水解法制备白头翁皂苷B₅的C-28位脱糖衍生物，探究白头翁皂苷B₅及其衍生物对脂多糖（LPS）诱导的急性肾损伤小鼠的药效学作用。方法 通过α-L鼠李糖苷酶水解白头翁皂苷B₅，分离纯化后得到其衍生物，采用ip LPS致雄性BALB/c小鼠急性肾损伤模型。将70只小鼠随机分为对照组、模型组、地塞米松（DEX，阳性药，5 mg·kg^-1）和白头翁皂苷 B₅低、高剂量（20、40 mg·kg^-1）组及白头翁皂苷 B₅衍生物低、高剂量（20、40 mg·kg^-1）组，每组 10只，造模前 2 h和造模后6 h给药。末次给药后6 h摘眼球取血，全自动生化仪计数血液中的白细胞（WBC）和中性粒细胞（Neu）；试剂盒法测定血清中肌酐（CRE）和尿素氮（BUN）水平；ELISA法检测血清和肾组织中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）水平；苏木素-伊红（HE）检测肾组织病理变化。结果 与模型组相比，白头翁皂苷 B₅组及其衍生物组小鼠的血清 WBC、Neu、CRE、BUN水平及血清和肾组织中 TNF- α、 IL-6、 IL-1β水平均显著降低（P＜0.05、0.01、0.001），肾组织损伤明显减轻。与白头翁皂苷B₅组相比，相同剂量下，白头翁皂苷B₅衍生物组可显著降低WBC、Neu和BUN的数量（P＜0.05、0.01、0.001）；在低剂量下可明显抑制小鼠血清中CRE的水平（P＜0.001）和肾组织中IL-6、IL-1β的释放（P＜0.001）；在高剂量下显著改善肾脏病理损伤程度。结论 白头翁皂苷B₅及其衍生物可以减轻由LPS诱导的急性肾损伤小鼠的肾脏组织损伤程度，相同剂量下，白头翁皂苷B₅的C-28位脱糖衍生物药效优于白头翁皂苷B₅。

Objective To synthesize C-28 deglycosylated derivative of hederasaponin C via enzymatic hydrolysis, and to assess their effects on lipopolysaccharide-induced acute kidney injury in mice.Methods Hederasaponin C was hydrolyzed by α-L rhamnosidase, and its derivative were obtained after separation and purification. Male BALB/c mice were injected intraperitoneally with lipopolysaccharide (LPS) to induce glomerulonephritis. Seventy mice were randomly divided into control group, model group, dexamethasone positive drug group, hederasaponin C low and high dose (20, 40 mg·kg^-1) groups, hederasaponin C derivative low and high dose (20, 40 mg·kg^-1) groups. 10 mice in each group were given the drug 2 h before modeling and 6 h after modeling. Blood samples were collected from the eyeballs 6 h after the last administration. WBC and Neu were counted by automatic biochemical analyzer. The reagent kit method was used to measure the levels of animal serum creatinine (CRE) and urea nitrogen (BUN). The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in serum and kidney were detected by ELISA. Hematoxylin-eosin (HE) was used to detect pathological changes in renal tissues.Results Compared to the model group, the counts of WBC, Neu, CRE, BUN and TNF-α, IL-6 and IL-1β in serum and kidney tissue of hederasaponin C group and its derivative group were significantly decreased (P < 0.05, 0.01, and 0.001), and renal tissue injury was significantly reduced. Compared with hederasaponin C group, the counts of WBC, Neu and BUN in hederasaponin C derivative group significantly decreased at the same dose (P < 0.05, 0.01, and 0.001). At low dose, CRE levels in serum and the release of IL-6 and IL-1β in renal tissue were significantly inhibited (P < 0.001). The degree of renal pathological injury was significantly improved at high dose.Conclusion Both hederasaponin C and its C-28 deglycosylation derivative can attenuate LPS-induced renal tissue damage in mice, with the derivative demonstrating enhanced efficacy at equivalent dosages. At the same dose, the efficacy of the C-28 desugarated derivative of hederasaponin C was better than that of hederasaponin C.

R285.5

广西研究生联合培养基地（桂学位〔2021〕6号）