目的 酶水解法制備白頭翁皂苷B₅的C-28位脫糖衍生物，探究白頭翁皂苷B₅及其衍生物對脂多糖（LPS）誘導的急性腎損傷小鼠的藥效學作用。方法 通過α-L鼠李糖苷酶水解白頭翁皂苷B₅，分離純化后得到其衍生物，采用ip LPS致雄性BALB/c小鼠急性腎損傷模型。將70只小鼠隨機分為對照組、模型組、地塞米松（DEX，陽性藥，5 mg·kg^-1）和白頭翁皂苷 B₅低、高劑量（20、40 mg·kg^-1）組及白頭翁皂苷 B₅衍生物低、高劑量（20、40 mg·kg^-1）組，每組 10只，造模前 2 h和造模后6 h給藥。末次給藥后6 h摘眼球取血，全自動生化儀計數(shù)血液中的白細胞（WBC）和中性粒細胞（Neu）；試劑盒法測定血清中肌酐（CRE）和尿素氮（BUN）水平；ELISA法檢測血清和腎組織中腫瘤壞死因子-α（TNF-α）、白細胞介素-6（IL-6）、白細胞介素-1β（IL-1β）水平；蘇木素-伊紅（HE）檢測腎組織病理變化。結(jié)果 與模型組相比，白頭翁皂苷 B₅組及其衍生物組小鼠的血清 WBC、Neu、CRE、BUN水平及血清和腎組織中 TNF- α、 IL-6、 IL-1β水平均顯著降低（P＜0.05、0.01、0.001），腎組織損傷明顯減輕。與白頭翁皂苷B₅組相比，相同劑量下，白頭翁皂苷B₅衍生物組可顯著降低WBC、Neu和BUN的數(shù)量（P＜0.05、0.01、0.001）；在低劑量下可明顯抑制小鼠血清中CRE的水平（P＜0.001）和腎組織中IL-6、IL-1β的釋放（P＜0.001）；在高劑量下顯著改善腎臟病理損傷程度。結(jié)論 白頭翁皂苷B₅及其衍生物可以減輕由LPS誘導的急性腎損傷小鼠的腎臟組織損傷程度，相同劑量下，白頭翁皂苷B₅的C-28位脫糖衍生物藥效優(yōu)于白頭翁皂苷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

廣西研究生聯(lián)合培養(yǎng)基地（桂學位〔2021〕6號）