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[摘要]
目的 比較血必凈注射液(XBJ)iv和ig給藥防治膿毒癥的藥效特點,為XBJ口服創(chuàng)新中藥研發(fā)提供參考。方法 采用盲腸結扎穿孔(CLP)法制備大鼠膿毒癥模型,ip脂多糖(LPS)法制備小鼠膿毒癥模型,分別于造模后0、12、24、36、48、60 h利用iv和ig 2種方式給予XBJ(4 mL·kg-1),比較2種給藥方式對膿毒癥模型動物死亡率的影響;通過肺濕質(zhì)量/干質(zhì)量、肺組織炎癥因子——腫瘤壞死因子-α(TNF-α)、白細胞介素-1β(IL-1β)水平測定,比較2種給藥方式對LPS誘導膿毒癥急性肺損傷(ALI)的影響;通過HE染色、FITC透過實驗考察2種給藥方式對LPS誘導膿毒癥小鼠腸屏障功能的影響。結果 與模型組比較,XBJ iv和ig給藥均可降低膿毒癥實驗動物死亡率,在CLP大鼠模型中,iv給藥效果優(yōu)于ig給藥,而在LPS小鼠模型中,ig給藥效果優(yōu)于iv給藥。與模型組比較,XBJ ig組和XBJ iv組小鼠的肺濕質(zhì)量/干質(zhì)量顯著降低(P<0.05);XBJ iv組肺組織中TNF-α、IL-1β水平顯著降低(P<0.01、0.001),XBJ ig組肺組織中TNF-α水平顯著降低(P<0.001);LPS造模后6、12 h,XBJ ig組小鼠血清FITC濃度顯著降低(P<0.05、0.01),XBJ iv組小鼠血清FITC濃度無明顯變化;XBJ ig較XBJ iv具有更優(yōu)改善膿毒癥小鼠回腸病理改變的作用。結論 XBJ iv和ig給藥均對膿毒癥有明確的治療作用,iv給藥具有保護膿毒癥ALI的藥效特點,而ig給藥具有改善膿毒癥腸屏障功能障礙的藥效特點。
[Key word]
[Abstract]
Objective To compare the efficacy difference and characteristics of intravenous and oral administration of Xuebijing Injection (XBJ) in the prevention and treatment of sepsis, so as to provide data reference for the development of oral innovative traditional Chinese medicine of XBJ. Methods A rat sepsis model was prepared using cecal ligation and perforation (CLP) method, and a mouse sepsis model was prepared using ip lipopolysaccharide (LPS) method. XBJ (4 mL·kg-1) was administered iv and ig at 0, 12, 24, 36, 48, and 60 h after modeling. The effects of the two administration methods on the mortality rate of sepsis model animals were compared. Through lung wet mass/dry mass, lung tissue inflammatory factor - tumor necrosis factor-α (TNF-α), Interleukin-1 β (IL-1β) level determination, comparing the effects of two administration methods on LPS induced sepsis induced acute lung injury (ALI). The effects of two administration methods on intestinal barrier function in LPS induced sepsis mice were investigated through HE staining and FITC experiments. Results Compared with the model group, both iv and ig administration can reduce the mortality rate of sepsis experimental animals. In the CLP rat model, iv administration has a better effect than ig administration, while in the LPS mouse model, ig administration has a better effect than iv administration. Compared with the model group, the lung wet mass/dry mass of XBJ ig group and XBJ iv group mice were significantly reduced (P < 0.05). TNF-α and IL-1β levels in lung tissue of XBJ iv group significant decrease (P < 0.01, 0.001),The level of TNF-α in lung tissue of XBJ ig group significantly decreased (P < 0.001). At 6 and 12 hours after LPS modeling, the serum FITC concentration of XBJ ig group mice significantly decreased (P < 0.05, 0.01), while there was no significant change in the serum FITC concentration of XBJ iv group. XBJ ig has a better effect on improving the pathological changes of the ileum in sepsis mice compared to XBJ iv. Conclusions Both intravenous administration and oral administration of XBJ have clear therapeutic effects on sepsis. Intravenous administration has the efficacy characteristics of protecting acute lung injury in sepsis, while oral administration has the efficacy characteristics of improving intestinal barrier dysfunction in sepsis.
[中圖分類號]
R285.5
[基金項目]