Hristova M, Yordanov M, Ivanovska N
Department of Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, 26 G. Bonchev Str., 1113 Sofia, Bulgaria.
Inflamm Res. 2003 Jan;52(1):1-7. doi: 10.1007/s000110300007.
To study the effect of the alkaloid fangchinoline on zymosan-induced multiple organ dysfunction syndrome (MODS) and Escherichia coli (E. coli)-induced septic shock.
Male ICR mice were used. Macrophages were isolated from peritoneal cavity for in vitro study.
Fangchinoline was administered i.p. at a dose of 1 or 5 mg/kg into the mice.
MODS was induced by intraperitoneal (i.p.) injection of zymosan at a dose 1.0 or 0.8/g b.w. E. coli-induced septic shock was provoked by i.p. inoculation of 5 x 10(8) bacterial cells into mice. TNF-alpha in serum and supernatants from peritoneal macrophages was detected by the use of L-929 cell cytotoxic assay. Alternative pathway (AP) complement activity was determined by hemolytic assay.
Fangchinoline increased the survival rate in lethal MODS and septic shock. The alkaloid prevented the loss of body weight and liver enlargement in MODS and suppressed serum tumor necrosis factor-alpha (TNF-alpha) accumulation in MODS and septic shock.
The result suggest that fangchinoline due mainly to its ability to downregulate TNF-alpha production might have protective effect in murine models of zymosan-induced MODS and E. coli-induced septic shock.
研究生物碱粉防己碱对酵母聚糖诱导的多器官功能障碍综合征(MODS)和大肠杆菌诱导的脓毒症休克的影响。
使用雄性ICR小鼠。从腹腔分离巨噬细胞用于体外研究。
将粉防己碱以1或5mg/kg的剂量腹腔注射给小鼠。
通过腹腔注射1.0或0.8/g体重的酵母聚糖诱导MODS。通过向小鼠腹腔接种5×10⁸个细菌细胞引发大肠杆菌诱导的脓毒症休克。使用L-929细胞细胞毒性测定法检测血清和腹腔巨噬细胞上清液中的肿瘤坏死因子-α(TNF-α)。通过溶血测定法测定替代途径(AP)补体活性。
粉防己碱提高了致死性MODS和脓毒症休克的存活率。该生物碱可防止MODS中体重减轻和肝脏肿大,并抑制MODS和脓毒症休克中血清肿瘤坏死因子-α(TNF-α)的积累。
结果表明,粉防己碱主要因其下调TNF-α产生的能力,可能对酵母聚糖诱导的MODS和大肠杆菌诱导的脓毒症休克小鼠模型具有保护作用。