發(fā)布時間：2018-10-25 14:06

【摘要】：目的探討積雪草酸(AA)預(yù)處理對膿毒癥小鼠急性腎損傷的作用及機制。方法選擇雄性BALB/c小鼠24只,隨機分為空白對照組、脂多糖(LPS)組、AA低劑量組、AA高劑量組各6只。AA低劑量組、AA高劑量組每天分別以AA 10、30 mg/kg灌胃預(yù)處理,空白對照組、LPS組每天以等量的0.5%羧甲基纖維素鈉灌胃。第3天灌胃2 h后,空白對照組腹腔注射PBS,其余三組腹腔注射LPS 10 mg/kg建立小鼠膿毒癥模型。各組于第3天腹腔注射4 h后,采用二乙酰肟比色法檢測血清尿素氮(BUN)水平;取腎組織,行HE染色觀察腎組織病理變化;采用real-time PCR法檢測炎癥因子(TNF-α、IL-1β、IL-6)及Notch信號通路相關(guān)基因(Notch1~4、Dll4、Jag2)表達。結(jié)果LPS組、AA低劑量組、AA高劑量組血清BUN水平均高于空白對照組,AA低劑量組、AA高劑量組血清BUN水平均低于LPS組(P均0.05)。HE染色可見正常對照組小鼠腎組織正常;LPS組表現(xiàn)為腎小管壞死,內(nèi)皮細胞腫脹以及炎性細胞浸潤;AA低劑量組、AA高劑量組表現(xiàn)為內(nèi)皮細胞腫脹減輕、炎癥細胞浸潤減少,病理損傷較LPS組明顯減輕。LPS組TNF-α、IL-1β、IL-6 mRNA表達均高于空白對照組(P均0.05),AA低劑量組、AA高劑量組TNF-α、IL-1β、IL-6 mRNA表達均低于LPS組(P均0.05)。LPS組Notch信號相關(guān)基因Notch1、Notch2、Notch3、Notch4、Dll4及Jag2 mRNA表達均低于空白對照組(P均0.05),AA低劑量組、AA高劑量組Notch1、Notch2、Notch3、Notch4、Dll4及Jag2 mRNA表達均高于LPS組(P均0.05)。結(jié)論 AA預(yù)處理能夠明顯減輕膿毒癥小鼠的腎損傷,其機制可能與調(diào)控Notch信號通路發(fā)揮抗炎作用有關(guān)。
[Abstract]:Objective to investigate the effect and mechanism of (AA) pretreatment on acute renal injury in septic mice. Methods Twenty-four male BALB/c mice were randomly divided into control group, lipopolysaccharide (LPS) group, AA low dose group and AA high dose group. AA low dose group and AA high dose group were pretreated with AA 1030 mg/kg daily. In the blank control group, LPS group was treated with 0.5% sodium carboxymethyl cellulose per day. The sepsis model of mice was established by intraperitoneal injection of LPS 10 mg/kg into the control group after intraperitoneal injection of PBS, for 2 h on the 3rd day. The serum urea nitrogen (BUN) levels were measured by diacetyl oxime colorimetry and the pathological changes of renal tissues were observed by HE staining. The expression of TNF- 偽, IL-1 尾, IL-6 and Notch signaling pathway related genes (Notch1~4,Dll4,Jag2) were detected by real-time PCR assay. Results the levels of serum BUN in LPS group, AA low dose group and AA high dose group were all higher than those in blank control group, AA low dose group and AA high dose group were lower than LPS group (P0. 05). HE staining showed normal renal tissue in normal control group, and renal tubular necrosis was found in LPS group. Endothelial cell swelling and inflammatory cell infiltration were observed in AA low dose group and AA high dose group, while endothelial cell swelling and inflammatory cell infiltration decreased in AA high dose group, while endothelial cell swelling and inflammatory cell infiltration decreased in AA low dose group and AA high dose group. The expression of TNF- 偽, IL-1 尾 and IL-6 mRNA in LPS group was higher than that in blank control group (P 0.05), and TNF- 偽, IL-1 尾, IL-6 mRNA expression in AA high dose group was lower than that in LPS group (P 0.05). LPS group was lower than that in blank control group). The expression of Notch1,Notch2,Notch3,Notch4,Dll4 and Jag2 mRNA in low dose group and high dose group of AA were higher than that in LPS group (P 0. 05, P 0. 05). Conclusion AA pretreatment can significantly reduce renal injury in septic mice, and its mechanism may be related to the anti-inflammatory effect of regulating Notch signaling pathway.
【作者單位】： 江蘇大學附屬醫(yī)院;
【基金】：國家自然科學基金資助項目(81301657) 江蘇省自然科學基金資助項目(BK20130476)
【分類號】：R459.7

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