人参皂苷Rg1对大鼠海水淹溺性肺损伤的保护作用及其机制

 目的 探讨人参皂苷Rg1对海水淹溺性肺损伤的保护作用及其机制。方法 128只雄性SD大鼠随机均分为4组:空白对照组(C组)、生理盐水组(S 组)、20 mg/kg低剂量人参皂甙Rg1组(L组)、100 mg/kg高剂量人参皂苷Rg1组(H组)。L组和H组分别经尾静脉注射人参皂苷20或100 mg/kg, S组尾静脉注射等容的生理盐水,给药2 h后建立海水淹溺性肺损伤模型。分别于吸入海水前(基础值T0)、吸入海水后30 min(T₁)、1 h(T₂)、2 h(T₃)和4 h(T₄)各时间点检测动脉血PaO₂和PaCO₂的动态变化;于建模后2 h和4 h取出肺组织和外周血标本,检测肺湿干重比(W/D)、肺泡灌洗液蛋白定量(BALF)、超氧化物歧化酶(SOD)和髓过氧化物酶(MPO)活性、丙二醛(MDA)和细胞因子TNF-α、IL-1β、IL-6的浓度,取建模后4 h的右肺下叶组织行HE病理检查。结果 T₀时4组的动脉血 PaO₂、PaCO₂差异均无统计学意义。T₁~T₄时S和L组PaO₂明显低于 H组(P<0.05),S和L组PaCO₂明显高于H组(P<0.05)。T₃和T₄时,S、L和H组肺组织 W/D比值均明显高于C组(P<0.05),H 组肺组织 W/D明显低于S组和L组(P<0.05)。H 组 MDA浓度和MPO活性明显低于S组和 L组(P<0.05), H 组SOD活性明显高于S组和 L组(P<0.05)。H 组血清中炎性因子TNF-α、IL-1β和IL-6水平明显低于S组和L组。HE病理染色显示H 组肺泡塌陷、水肿及炎性细胞浸润较S组明显减轻。结论 预防性使用人参皂苷Rg1(100 mg/kg)能显著减轻海水淹溺导致的早期(4 h内)肺损伤,其保护机制与减轻肺内的炎性反应和氧化应激相关。

Protective effects of ginsenoside Rg1 on sea water drowning induced lung injury in rats

Objective To determine the protective effects and potential mechanisms of ginsenoside Rg1 on lung injury induced by sea water drowning.Methods One hundred and twenty-eight male SD rats were randomly divided into four groups: the control group (group C), sea water+saline group (group S), sea water group+20 mg/kg Rg1(group L) and sea water group+100 mg/kg Rg1(group H). Rats were intravenously injected with different doses of Rg1 or saline before a standard model of sea water drowning was established in group S, L and H. The arterial PaO₂, PaCO₂, wet to dry weight ratio(W/D), protein concentrations of bronchoalveolar lavage fluid (BALF), MDA, SOD and MPO activity, cytokines expressions and histological changes were measured at the following time points as designated:before drowning(T₀) and 30 min(T₁), 1 h (T₂), 2 h(T₃) and 4 h(T₄) after drowning.Results PaO₂ at T₁,T₂,T₃ and T₄ in group S and L was significantly lower than in group H (P<0. 05), but PaCO₂ was significantly higher(P<0. 05).No significant difference was observed between group S and group L. The W/D ratio, BALF protein concentration, MDA and MPO activity were significantly higher in group S and L than in group H at T₃ and T₄(P<0.05). The activity of SOD in group S and L was significantly lower than in group H(P<0 05). Compared with group S, the expressions of such cytokines as TNF-α, IL-1β and IL-6 were significantly decreased. HE staining showed severe alveolar rupture, edema, and inflammatory cell infiltration in group S.Conclusions Pretreatment with Rg1 can effectively protect rats from sea water drowning induced lung injury in the early stage(within 4 hours). The underlying mechanism is possibly associated with the suppression of inflammatory responses and oxidative stress.