本文關(guān)鍵詞： 硫辛酸 LPS 肝臟 mtDNA　出處：《南京農(nóng)業(yè)大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

【摘要】：在目前的規(guī)�；B(yǎng)豬場(chǎng)中,炎癥感染不可避免的經(jīng)常存在。炎癥可以引起不可逆肝損傷。因此抑制肝臟的炎癥對(duì)于機(jī)體的健康異常重要。α-硫辛酸(LA),一種天然的短鏈脂肪酸,也是線粒體中丙酮酸脫氫酶復(fù)合體和α-酮戊二酸脫氫酶復(fù)合體的輔酶。它在線粒體代謝當(dāng)中發(fā)揮重要作用,但LA是否可以通過影響線粒體功能來緩解炎癥引起的肝臟損傷,以及其可能的機(jī)制并不清楚。此外,對(duì)于豬的炎癥感染研究,大多數(shù)研究都關(guān)注在免疫反應(yīng),鮮少有研究關(guān)注豬肝臟線粒體的功能變化。因此,在本研究分兩部分:第一部分以小鼠為模型,探討炎癥狀況下,LA對(duì)肝臟線粒體的作用以及機(jī)制;第二部分以生長(zhǎng)豬為模型,探討炎癥對(duì)于豬肝臟線粒體的影響。1 LA對(duì)LPS引起的小鼠肝臟線粒體損傷的緩解作用及其機(jī)制以小鼠為模型,隨機(jī)分為三組:Con組注射5d生理鹽水;LPS組注射5d生理鹽水,并在第五天注射1h后注射5mg/kgLPS;LA+LPS組注射5d100mg/kg的LA,并同樣在第五天注射1h后注射5mg/kgLPS。6h,24h后采樣,檢測(cè)肝臟損傷,能量代謝和線粒體功能以及調(diào)控。結(jié)果顯示,相對(duì)于LPS組,LA下調(diào)了血漿中谷丙轉(zhuǎn)氨酶和谷草轉(zhuǎn)氨酶含量,緩解了肝臟損傷。肝臟ATP、NADH含量,大多數(shù)線粒體DNA(mtDNA)編碼基因的基因表達(dá),以及線粒體復(fù)合物I,IV和V活性也都相對(duì)于LPS組顯著上調(diào)。去乙憸化酶3(Sirt 3)對(duì)于調(diào)節(jié)線粒體代謝至關(guān)重要,LA同樣上調(diào)了 Sirt 3的表達(dá)。關(guān)于mtDNA編碼基因表達(dá)的調(diào)控,本研究表明mtDNAD-loop區(qū)域的甲基化水平?jīng)]有變化。然而,相對(duì)于LPS組,LA上調(diào)了糖皮質(zhì)激素受體(GR)在肝臟的蛋白表達(dá),同時(shí)也上調(diào)了 GR在mtDNA D-loop區(qū)域的結(jié)合。以上結(jié)果表明在炎癥狀態(tài)下,LA通過提高線粒體功能來發(fā)揮肝臟保護(hù)作用,GR通過上調(diào)其在mtDNA D-loop區(qū)域的結(jié)合參與了此過程。2 LPS對(duì)豬肝臟線粒體功能的影響以生長(zhǎng)豬為模型,隨機(jī)分為兩組:Con組注射生理鹽水,LPS組注射15 μg/kg LPS,6h后采樣檢測(cè)肝臟損傷,能量代謝以及線粒體功能。結(jié)果顯示,LPS處理后血漿谷草轉(zhuǎn)氨酶含量顯著上調(diào),引起豬肝臟損傷。且炎癥因子TNF-α,NF-κB和IL-1α在肝臟中基因表達(dá)顯著上調(diào)。雖然肝臟中甘油三酯和糖原含量顯著下調(diào),能量消耗增加,但是肝臟中ATP、ADP和AMP以及能荷均沒有受到LPS的影響。并且在本研究炎癥狀態(tài)下,mtDNA編碼基因的表達(dá)以及線粒體復(fù)合物IV和V的活力也沒有發(fā)生顯著變化。
[Abstract]:In the current large-scale pig farms, inflammatory infection is inevitable. Inflammation can cause irreversible liver damage. Therefore, inhibiting liver inflammation is extremely important for the health of the body. 偽 -lipoxylic acid (偽 -lipoic acid). A natural short-chain fatty acid, also a coenzyme of pyruvate dehydrogenase complex and 偽 -ketoglutarate dehydrogenase complex in mitochondria, which plays an important role in mitochondrial metabolism. However, it is not clear whether LA can alleviate liver injury caused by inflammation by affecting mitochondrial function and its possible mechanism. In addition, most studies on inflammatory infection in pigs focus on immune response. Few studies have focused on the functional changes of hepatic mitochondria in pigs. Therefore, this study is divided into two parts: the first part is a mouse model to explore the effect and mechanism of LA on liver mitochondria under inflammatory condition; In the second part, the effects of inflammation on the mitochondria of pig liver were studied in order to investigate the effects of inflammation on mitochondria damage induced by LPS in mice and its mechanism. They were randomly divided into three groups: the control group was injected with saline for 5 days. In LPS group, normal saline was injected for 5 days, and 5 mg / kg LPS was injected 1 hour after injection on 5th days. The LA LPS group was injected with 5 d 100 mg / kg LA. the same time was injected 1 h on day 5th, and then injected 5 mg / kg LPS.6 h for 24 h, then the liver injury was detected. Energy metabolism, mitochondrial function and regulation. The results showed that LA decreased plasma alanine aminotransferase and alanine aminotransferase contents, and alleviated liver injury and liver ATP compared with LPS group. The NADH content, the gene expression of most mtDNA-encoded genes, and the activities of mitochondrial complex IIV and V were also significantly increased compared with those of LPS group. 皙The expression of Sirt 3 was also upregulated by LA, which was important for regulating mitochondrial metabolism. The regulation of mtDNA coding gene expression was also discussed. This study showed that the methylation level in the mtDNAD-loop region did not change. However, LA upregulated the expression of glucocorticoid receptor GRG in the liver compared with the LPS group. The binding of gr to mtDNA D-loop region was also up-regulated. The above results suggest that LA plays a role in liver protection by improving mitochondrial function in inflammatory state. Gr participated in this process by upregulating its binding to mtDNA D-loop region. 2. 2 LPS was involved in the effect of GR on the function of hepatic mitochondria in pigs. The rats were randomly divided into two groups: control group (n = 10) and LPS group (n = 6). Liver injury, energy metabolism and mitochondrial function were measured after injection of 15 渭 g / kg LPSN for 6 h. Plasma glutamic oxaloacetic transaminase content was significantly up-regulated after LPS treatment, resulting in liver injury and inflammatory factor TNF- 偽. The gene expression of NF- 魏 B and IL-1 偽 was significantly up-regulated in the liver. Although the contents of triglyceride and glycogen decreased significantly and the energy consumption increased in the liver, ATP was found in the liver. ADP, AMP and energy charge were not affected by LPS. The expression of mtDNA coding gene and the activity of mitochondrial complexes IV and V did not change significantly.
【學(xué)位授予單位】：南京農(nóng)業(yè)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：S852.3

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 劉振山;馮云;薛志剛;范國(guó)平;;線粒體DNA與DNA甲基化[J];生物學(xué)雜志;2013年05期

2 Yu-Feng Tian;Chih-Tsueng He;Yu-Ting Chen;Po-Shiuan Hsieh;;Lipoic acid suppresses portal endotoxemia-induced steatohepatitis and pancreatic inflammation in rats[J];World Journal of Gastroenterology;2013年18期

3 呂震;張友祥;;肝硬化腸源性內(nèi)毒素血癥臨床研究現(xiàn)狀[J];肝臟;2011年03期

4 溫璐璐;鄧新;張曉雯;;內(nèi)毒素與肝纖維化的研究進(jìn)展[J];中國(guó)醫(yī)療前沿;2010年02期

5 張雪梅;丁惠國(guó);;線粒體損傷與肝臟疾病[J];中國(guó)實(shí)用內(nèi)科雜志;2009年S2期

6 田芳;仲偉鑒;;α-硫辛酸的抗氧化和促氧化雙向作用[J];環(huán)境與職業(yè)醫(yī)學(xué);2008年01期

7 馬慧敏;周安國(guó);王之盛;馬志勇;;硫辛酸的抗氧化功能及其在動(dòng)物生產(chǎn)上的應(yīng)用現(xiàn)狀[J];飼料工業(yè);2006年22期

8 李曉東;徐建良;盛國(guó)光;姜楠;;內(nèi)毒素血癥對(duì)大鼠肝細(xì)胞線粒體能量代謝的影響及黃芪注射液的干預(yù)作用[J];中國(guó)中西醫(yī)結(jié)合消化雜志;2006年04期

9 汪泰初;劉朝良;肖林珍;;線粒體基因組(mtDNA)的研究進(jìn)展[J];安徽農(nóng)業(yè)科學(xué);2006年10期

10 余林中;江愛達(dá);陳育堯;林慧;秦清和;馬曉冬;;涼膈散對(duì)內(nèi)毒素血癥小鼠的肝臟庫普弗細(xì)胞CD14和清道夫受體表達(dá)的影響[J];中國(guó)中藥雜志;2006年03期

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