白藜蘆醇對膿毒癥大鼠急性腎損傷的保護作用及其機制
發(fā)布時間：2019-03-16 10:01
【摘要】：膿毒癥并發(fā)急性腎損傷(AKI)是膿毒癥患者死亡率居高不下的重要原因,腎組織炎癥因子的瀑布式釋放及炎癥反應的增強在AKI的發(fā)生中起重要作用。核轉錄因子-κB(NF-κB)是炎癥相關基因關鍵的轉錄調節(jié)因子,活化后可誘導多種炎癥因子的轉錄合成,而內質網應激(ERS)介導了NF-κB炎癥信號通路。白藜蘆醇是一種具有強大抗炎活性的多酚化合物,其抗炎作用與抑制NF-κB的活性有關,但是是否與緩解ERS有關目前尚無研究報道。因此,本研究旨在以"ERS/NF-κB"通路為切入點,探討白藜蘆醇對膿毒癥時急性腎損傷的保護作用及其機制。 本實驗首先采用盲腸結扎穿刺術(CLP)建立膿毒癥大鼠模型,將108只雄性SD大鼠隨機分為A、B、C三大組：A組為生存率觀察組,B組為6小時白藜蘆醇干預組,C組為12小時白藜蘆醇干預組。每組再分為四個小組：(1)假手術組(Sham組)；(2)腹腔注射30mg/kg白藜蘆醇的假手術組(Sham+Res組)；(3)膿毒癥模型組(CLP組)；(4)腹腔注射30mg/kg白藜蘆醇的膿毒癥模型組(CLP+Res組)。術后主要觀察指標：大鼠的生存情況,腎組織的形態(tài)學變化,血肌酐和尿素氮水平,腎臟組織中葡萄糖調節(jié)蛋白78(GRP78)/免疫球蛋白重鏈結合蛋白(BiP)、需肌醇酶(IRE-1)和p65的表達情況；腎組織和血清中TNF-α、IL-1p、IL-6和IL-10的mRNA和蛋白表達水平。 結果顯示：(1)以術后72小時為大鼠存活與否的標準,sham組和sham+Res組大鼠的存活率均為100%,CLP組大鼠的存活率約40%,較假手術明顯降低(P0.05),而白藜蘆醇可顯著提高CLP的存活率(P0.05),約65%。(2)術后12小時,CLP組大鼠的血清肌酐和尿素氮水平均較Sham組顯著升高(P0.05),白藜蘆醇可顯著降低CLP血清肌酐和尿素氮的水平(P0.05),但對假手術大鼠無明顯影響。此外白藜蘆醇可顯著減輕CLP大鼠腎小管明顯腫脹,管腔變小的表現。(3)術后12小時,白藜蘆醇可顯著降低CLP大鼠腎組織中GRP78/Bip、磷酸化IRE-1和p65蛋白的高表達(P0.05)。Sham組和Sham+Res組p65主要定位于細胞漿,CLP組p65主要定位于細胞核,而白藜蘆醇處理的CLP大鼠p65的細胞定位以胞漿為主。(4)術后6、12小時,白藜蘆醇均可顯著降低CLP大鼠腎組織中TNF-α、IL-1β、IL-6mRNA的高表達(P0.05),但其對CLP大鼠腎組織中IL-10mRNA的表達均無明顯影響(p0.05)。(5)術后6小時,白藜蘆醇可顯著降低CLP大鼠血清TNF-α、IL-1β和IL-6的含量(P均0.05),但對IL-10含量無明顯影響。術后12小時,白藜蘆醇不僅顯著降低CLP大鼠血清TNF-α、IL-1p和IL-6的含量,且明顯增加CLP大鼠血清IL-10含量(P均0.05)。 綜上所述,本研究結果表明：白藜蘆醇可顯著降低膿毒癥大鼠的死亡率,減輕急性腎損傷,這可能與其緩解內質網應激,抑制NF-κB通路活化,降低腎組織炎癥反應的作用有關。
[Abstract]:(AKI) is an important cause of high mortality in sepsis patients with acute renal injury. Waterfall release of inflammatory factors in renal tissue and enhancement of inflammatory reaction play an important role in the development of AKI. Nuclear transcription factor-魏 B (NF- 魏 B) is a key transcription regulator of inflammation-associated genes. Activation can induce transcription synthesis of a variety of inflammatory factors, while endoplasmic reticulum stress (ERS) mediates NF- 魏 B inflammatory signaling pathway. Resveratrol is a kind of polyphenol compound with strong anti-inflammatory activity. Its anti-inflammatory effect is related to the inhibition of NF- kappa B activity, but there is no report on whether resveratrol is related to the alleviation of ERS. Therefore, the aim of this study was to explore the protective effect of resveratrol on acute renal injury induced by sepsis and the mechanism of resveratrol through "ERS/NF- kappa B" pathway. In this experiment, a rat model of sepsis was established by cecal ligation and puncture (CLP). 108 male SD rats were randomly divided into three groups: group A (survival rate), group B (resveratrol intervention for 6 hours), group A (survival rate) and group B (resveratrol intervention for 6 hours). Group C was treated with resveratrol for 12 hours. Each group was subdivided into four groups: (1) sham operation group (Sham group); (2), sham operation group with 30mg/kg resveratrol injected intraperitoneally, (Sham Res group); (3, sepsis model group (CLP group); (4) 30mg/kg resveratrol model group (CLP Res group). Main outcome measures: survival of rats, morphological changes of renal tissue, levels of serum creatinine and urea nitrogen, glucose-regulated protein 78 (GRP78) / immunoglobulin heavy chain binding protein (BiP), in renal tissue Expression of inositase (IRE-1) and p65; MRNA and protein expression levels of TNF- 偽, IL-1p,IL-6 and IL-10 in kidney and serum. The results showed: (1) the survival rate of rats in sham group and sham Res group was 100% and 40% respectively, which was significantly lower than that in sham operation (P0.05), taking 72 hours after operation as the standard for survival or not of rats, and the survival rates of rats in sham Res group and CLP group were 100% and 40%, respectively (P0.05). Resveratrol significantly increased the survival rate of CLP (P0.05), about 65%. (2) 12 hours after operation, the serum creatinine and urea nitrogen water in CLP group were significantly higher than those in Sham group (P0.05). Resveratrol significantly decreased the levels of serum creatinine and urea nitrogen in CLP (P0.05), but had no significant effect on sham-operated rats. In addition, resveratrol could significantly reduce the swelling of renal tubules and the decrease of lumen in CLP rats. (3) 12 hours after operation, resveratrol significantly decreased GRP78/Bip, in renal tissue of CLP rats. The high expression of phosphorylated IRE-1 and p65 protein (P0.05) was mainly localized in cytoplasm in). Sham group and Sham Res group, while p65 was mainly localized in nucleus in CLP group. (4) 6 hours and 12 hours after operation, resveratrol significantly decreased the high expression of TNF- 偽, IL-1 尾 and IL-6mRNA in renal tissue of CLP rats treated with resveratrol (P0.05). However, resveratrol had no significant effect on the expression of IL-10mRNA in renal tissue of CLP rats (p0.05). (5). Resveratrol significantly decreased the levels of TNF- 偽, IL-1 尾 and IL-6 in serum of CLP rats 6 hours after operation (P0.05). (5), and resveratrol significantly decreased the contents of TNF- 偽, IL-1 尾 and IL-6 in serum of CLP rats. But it had no obvious effect on the content of IL-10. 12 hours after operation, resveratrol not only significantly decreased the levels of serum TNF- 偽, IL-1p and IL-6 in CLP rats, but also significantly increased the content of serum IL-10 in CLP rats (all P0.05). In conclusion, the results showed that resveratrol could significantly reduce the mortality and acute renal injury in sepsis rats, which might be related to the release of endoplasmic reticulum stress and the inhibition of NF- kappa B pathway activation. The effect of reducing the inflammatory reaction of renal tissue is related.
【學位授予單位】：中南大學
【學位級別】：碩士
【學位授予年份】：2013
【分類號】：R459.7
本文編號：2441155
[Abstract]:(AKI) is an important cause of high mortality in sepsis patients with acute renal injury. Waterfall release of inflammatory factors in renal tissue and enhancement of inflammatory reaction play an important role in the development of AKI. Nuclear transcription factor-魏 B (NF- 魏 B) is a key transcription regulator of inflammation-associated genes. Activation can induce transcription synthesis of a variety of inflammatory factors, while endoplasmic reticulum stress (ERS) mediates NF- 魏 B inflammatory signaling pathway. Resveratrol is a kind of polyphenol compound with strong anti-inflammatory activity. Its anti-inflammatory effect is related to the inhibition of NF- kappa B activity, but there is no report on whether resveratrol is related to the alleviation of ERS. Therefore, the aim of this study was to explore the protective effect of resveratrol on acute renal injury induced by sepsis and the mechanism of resveratrol through "ERS/NF- kappa B" pathway. In this experiment, a rat model of sepsis was established by cecal ligation and puncture (CLP). 108 male SD rats were randomly divided into three groups: group A (survival rate), group B (resveratrol intervention for 6 hours), group A (survival rate) and group B (resveratrol intervention for 6 hours). Group C was treated with resveratrol for 12 hours. Each group was subdivided into four groups: (1) sham operation group (Sham group); (2), sham operation group with 30mg/kg resveratrol injected intraperitoneally, (Sham Res group); (3, sepsis model group (CLP group); (4) 30mg/kg resveratrol model group (CLP Res group). Main outcome measures: survival of rats, morphological changes of renal tissue, levels of serum creatinine and urea nitrogen, glucose-regulated protein 78 (GRP78) / immunoglobulin heavy chain binding protein (BiP), in renal tissue Expression of inositase (IRE-1) and p65; MRNA and protein expression levels of TNF- 偽, IL-1p,IL-6 and IL-10 in kidney and serum. The results showed: (1) the survival rate of rats in sham group and sham Res group was 100% and 40% respectively, which was significantly lower than that in sham operation (P0.05), taking 72 hours after operation as the standard for survival or not of rats, and the survival rates of rats in sham Res group and CLP group were 100% and 40%, respectively (P0.05). Resveratrol significantly increased the survival rate of CLP (P0.05), about 65%. (2) 12 hours after operation, the serum creatinine and urea nitrogen water in CLP group were significantly higher than those in Sham group (P0.05). Resveratrol significantly decreased the levels of serum creatinine and urea nitrogen in CLP (P0.05), but had no significant effect on sham-operated rats. In addition, resveratrol could significantly reduce the swelling of renal tubules and the decrease of lumen in CLP rats. (3) 12 hours after operation, resveratrol significantly decreased GRP78/Bip, in renal tissue of CLP rats. The high expression of phosphorylated IRE-1 and p65 protein (P0.05) was mainly localized in cytoplasm in). Sham group and Sham Res group, while p65 was mainly localized in nucleus in CLP group. (4) 6 hours and 12 hours after operation, resveratrol significantly decreased the high expression of TNF- 偽, IL-1 尾 and IL-6mRNA in renal tissue of CLP rats treated with resveratrol (P0.05). However, resveratrol had no significant effect on the expression of IL-10mRNA in renal tissue of CLP rats (p0.05). (5). Resveratrol significantly decreased the levels of TNF- 偽, IL-1 尾 and IL-6 in serum of CLP rats 6 hours after operation (P0.05). (5), and resveratrol significantly decreased the contents of TNF- 偽, IL-1 尾 and IL-6 in serum of CLP rats. But it had no obvious effect on the content of IL-10. 12 hours after operation, resveratrol not only significantly decreased the levels of serum TNF- 偽, IL-1p and IL-6 in CLP rats, but also significantly increased the content of serum IL-10 in CLP rats (all P0.05). In conclusion, the results showed that resveratrol could significantly reduce the mortality and acute renal injury in sepsis rats, which might be related to the release of endoplasmic reticulum stress and the inhibition of NF- kappa B pathway activation. The effect of reducing the inflammatory reaction of renal tissue is related.
【學位授予單位】：中南大學
【學位級別】：碩士
【學位授予年份】：2013
【分類號】：R459.7
【參考文獻】
相關期刊論文 前4條
1 孫婷;劉曉立;寧方玉;李志;王濤;王曉芝;;連續(xù)性血液凈化對嚴重膿毒癥患者的治療作用[J];山東醫(yī)藥;2010年13期
2 吳立峰;方強;蘇群;李子龍;;液體復蘇對嚴重膿毒癥膿毒性休克患者全身氧代謝與組織灌注的影響[J];中國急救醫(yī)學;2006年07期
3 張_g;任延波;蔣麗;;膿毒癥早期大鼠腎臟細胞凋亡及炎癥細胞因子的變化[J];中國危重病急救醫(yī)學;2006年02期
4 蘇艷麗;王紅;張淑文;陰峧宏;文艷;王超;王寶恩;;中藥芪參活血顆粒治療重度膿毒癥的療效觀察[J];中國中西醫(yī)結合雜志;2008年03期
，本文編號：2441155
本文鏈接：http://sikaile.net/yixuelunwen/jjyx/2441155.html
最近更新
教材專著
