葛根素对SD大鼠全身炎症反应综合征的治疗作用及其机制研究

Study of the curative effect and mechanism of puerarin to the SIRS rats

目的建立全身炎症反应综合征(SIRS)SD大鼠模型,探讨葛根素对SIRS的治疗效果及其作用机制。方法采用腹腔注射酵母多糖-石蜡悬液制备SD大鼠SIRS模型。通过SIRS大鼠静脉注射葛根素后动物死亡率变化,了解葛根素治疗SD大鼠SIRS的效果。采用ELISA定量检测试剂盒,测定葛根素对SIRS大鼠外周血肿瘤坏死因子(TNF-α)、白介素6(IL-6)和白介素10(IL-10)水平的变化。结果注射剂量分别为750mg/kg和1000mg/kg酵母多糖-石蜡悬液时,均可诱导大鼠发生SIRS。腹腔注射1000mg/kg酵母多糖-石蜡悬液后48h,大鼠的死亡率为73.3%,但同时再静脉注射62.5mg/kg葛根素后死亡率可降至20.0%(P【0.01)。腹腔注射750mg/kg酵母多糖-石蜡悬液后24h和48h,大鼠外周血中TNF-α、IL-6和IL-10浓度分别为(32.89±5.58)pg/ml、(578.20±92.45)pg/ml、(1.35±0.21)ng/ml和(31.57±5.26)pg/ml、(546.15±89.45)pg/ml、(1.31±0.19)ng/ml,静脉注射62.5mg/kg葛根素后24h和48h的TNF-α、IL-6浓度分别降至(16.71±3.75)pg/ml、(385.30±76.34)pg/ml和(15.32±3.41)pg/ml、(363.29±68.59)pg/ml(P【0.01),IL-10浓度升至2.05±0.19ng/ml和2.08±0.20ng/ml(P【0.01)。结论本研究成功地建立了稳定的SIRS大鼠模型。葛根素对SIRS大鼠有良好治疗效果,下调促炎因子TNF-α和IL-6水平、上调抗炎因子IL-10水平可能是葛根素抗SIRS的作用机制之一。

Objective To establish rat model suffering from systemic inflammatory response syndrome (SIRS), and to determine the curative effect of puerarin to the SIRS and its mechanism.Methods A SIRS animal model in SD rat was established by the intraperitoneal injection with zymosan-paraffin suspension. According to the mortality change of the SIRS rats after intravenous injection with puerarin, the effect of puerarin to cure SIRS rats was determined. By using quantitative ELISA kits, the effect of puerarin to regulate the levels of TNF-α, IL-6 and IL-10 in peripheral blood of SIRS rats was demonstrated, and the perhaps mechanism was studied.Results The 750 mg/kg and 1000 mg/kg zymosan-paraffin suspension could induce the rats to generate SIRS, respectively. The mortality of the rats was 73.3% after 48 hours intraperitoneally injected with 1000 mg/kg zymosan-paraffin suspension. If the animals were intravenously injected with 62.5 mg/kg puerarin per rat, the mortality could decrease to 20.0% (P<0.01). After 24 and 48 hours of intraperitoneal injection with 750 mg/kg zymosan-paraffin suspension per rat, the concentrations of TNF-α, IL-6 and IL-10 in the animal peripheral blood were 32.89±5.58 pg/ml, 578.20±92.45 pg/ml, 1.35±0.21 ng/ml, and 31.57±5.26 pg/ml, 546.15±89.45 pg/ml, 1.31±0.19 ng/ml, respectively. If the animals were intravenously injected with 62.5 mg/kg puerarin per rat, the levels of TNF-α and IL-6 could decrease to 16.71±3.75 pg/ml, 385.30±76.34 pg/ml and 15.32±3.41 pg/ml, 363.29±68.59 pg/ml, respectively(P<0.01), and IL-10 increase to 2.05±0.19 ng/ml and 2.08±0.20 ng/ml, respectively(P<0.01).Conclusion A stable SIRS rat model is successfully established in this study. Puerarin has a fine curative effect to SIRS rats. Down-regulating the levels of inflammation-promoting factors TNF-α and IL-6 and up-regulating the level of inflammation-inhibiting factor IL-10 may be one of the mechanisms of puerarin against SIRS.