积雪草酸预处理对脓毒症小鼠急性肾损伤的影响及机制

发布时间：2018-10-25 14:06

【摘要】：目的探讨积雪草酸(AA)预处理对脓毒症小鼠急性肾损伤的作用及机制。方法选择雄性BALB/c小鼠24只,随机分为空白对照组、脂多糖(LPS)组、AA低剂量组、AA高剂量组各6只。AA低剂量组、AA高剂量组每天分别以AA 10、30 mg/kg灌胃预处理,空白对照组、LPS组每天以等量的0.5%羧甲基纤维素钠灌胃。第3天灌胃2 h后,空白对照组腹腔注射PBS,其余三组腹腔注射LPS 10 mg/kg建立小鼠脓毒症模型。各组于第3天腹腔注射4 h后,采用二乙酰肟比色法检测血清尿素氮(BUN)水平;取肾组织,行HE染色观察肾组织病理变化;采用real-time PCR法检测炎症因子(TNF-α、IL-1β、IL-6)及Notch信号通路相关基因(Notch1~4、Dll4、Jag2)表达。结果LPS组、AA低剂量组、AA高剂量组血清BUN水平均高于空白对照组,AA低剂量组、AA高剂量组血清BUN水平均低于LPS组(P均0.05)。HE染色可见正常对照组小鼠肾组织正常;LPS组表现为肾小管坏死,内皮细胞肿胀以及炎性细胞浸润;AA低剂量组、AA高剂量组表现为内皮细胞肿胀减轻、炎症细胞浸润减少,病理损伤较LPS组明显减轻。LPS组TNF-α、IL-1β、IL-6 mRNA表达均高于空白对照组(P均0.05),AA低剂量组、AA高剂量组TNF-α、IL-1β、IL-6 mRNA表达均低于LPS组(P均0.05)。LPS组Notch信号相关基因Notch1、Notch2、Notch3、Notch4、Dll4及Jag2 mRNA表达均低于空白对照组(P均0.05),AA低剂量组、AA高剂量组Notch1、Notch2、Notch3、Notch4、Dll4及Jag2 mRNA表达均高于LPS组(P均0.05)。结论 AA预处理能够明显减轻脓毒症小鼠的肾损伤,其机制可能与调控Notch信号通路发挥抗炎作用有关。
[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- 伪, 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- 伪, IL-1 尾 and IL-6 mRNA in LPS group was higher than that in blank control group (P 0.05), and TNF- 伪, 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.
【作者单位】：江苏大学附属医院;
【基金】：国家自然科学基金资助项目(81301657) 江苏省自然科学基金资助项目(BK20130476)
【分类号】：R459.7

【相似文献】