【摘要】：目的探討波動(dòng)性高糖在THP-1巨噬細(xì)胞中通過Toll樣受體4/c-Jun氨基末端激酶(TLR4/JNK)信號轉(zhuǎn)導(dǎo)通路對脂肪細(xì)胞脂肪酸結(jié)合蛋白(A-FABP)表達(dá)的影響。 方法將佛波酯(PMA)加入培養(yǎng)的THP-1人單核細(xì)胞株中,誘導(dǎo)細(xì)胞分化為THP-1巨噬細(xì)胞,分為以下幾組進(jìn)行干預(yù)：細(xì)胞培養(yǎng)液組,甘露醇組(20mmol/),恒定低糖組(5mmol/1)、恒定高糖組(20mmol/1)、脂多糖組(100ng/ml)、波動(dòng)性高糖1組(5mmol/l或20mmol/l,每12小時(shí)換液一次)、波動(dòng)性高糖2組(5mmol/l或20mmol/l,每8小時(shí)換液一次)。以上各組又分別加入磷酸化JNK抑制劑SP600125或空白載體,干預(yù)72小時(shí)后測定THP-1巨噬細(xì)胞上TLR4、細(xì)胞內(nèi)磷酸化JNK和A-FABP的表達(dá)水平,以及細(xì)胞上清液中IL-1β和TNF-α的表達(dá)水平。 結(jié)果恒定高糖組TLR4、細(xì)胞內(nèi)磷酸化JNK和A-FABP、TNF-α和IL-1β水平均較恒定低糖組升高。波動(dòng)性高糖組較恒定性高糖組更高,且波動(dòng)性高糖2組高于波動(dòng)性高糖1組(P均0.05)。加入磷酸化JNK抑制劑SP600125后,與加入空白載體組相比,THP-1巨噬細(xì)胞表達(dá)的TLR4蛋白以及mRNA水平變化差別沒有統(tǒng)計(jì)學(xué)意義(P均0.05),而磷酸化JNK、A-FABP蛋白和mRNA表達(dá)水平以及細(xì)胞上清液中TNF-α和IL-1β水平均降低,差異有統(tǒng)計(jì)學(xué)意義(P均0.05)。 結(jié)論高糖可以通過誘導(dǎo)THP-1巨噬細(xì)胞上TLR4/磷酸JNK信號通路的活化而促進(jìn)A-FABP的表達(dá)以及炎癥因子的釋放；與恒定性高糖相比,波動(dòng)性高糖能進(jìn)一步誘導(dǎo)THP-1巨噬細(xì)胞上TLR4／磷酸化JNK信號通路活化、A-FABP的表達(dá)以及炎癥因子的分泌。
[Abstract]:Aim to investigate the effect of volatile high glucose on the expression of fatty acid binding protein (A-FABP) in adipocytes through Toll-like receptor 4/c-Jun N-terminal kinase (TLR4/JNK) signal transduction pathway in THP-1 macrophages. Methods the cells were induced to differentiate into THP-1 macrophages by adding phorbol ester (PMA) into the cultured human monocytes of THP-1 and were divided into the following groups: cell culture solution group, mannitol group (20mmol/), and control group. Constant low glucose group (5mmol/1), constant high glucose group (20mmol/1), lipopolysaccharide group (100ng/ml), fluctuating high glucose group 1 (5mmol/l or 20 mmol / ml, every 12 hours), fluctuating high glucose group 2 (5mmol/l or 20 mmol / ml), Change fluid every 8 hours) The phosphorylated JNK inhibitor SP600125 or blank vector were added to the above groups. 72 hours after intervention, the expression levels of phosphorylated JNK and A-FABP in TLR4, cells were measured. And the expression of IL-1 尾 and TNF- 偽 in the supernatant. Results the levels of phosphorylated JNK and 偽-IL-1-偽 and IL-1-尾 in TLR4, cells were significantly higher than those in low glucose group (P < 0.05). The fluctuating high glucose group was higher than the constant high glucose group, and the fluctuating high glucose group 2 was higher than the fluctuating high glucose group 1 (all P 0.05). When phosphorylated JNK inhibitor SP600125 was added, there was no significant difference in the expression of TLR4 protein and mRNA in THP-1 macrophages compared with the blank vector group (P0.05), but the phosphorylated JNK, was not significantly different from that in the blank vector group (P0.05). The expression levels of A-FABP protein and mRNA and the levels of TNF- 偽 and IL-1 尾 in the supernatant were significantly lower than those in the control group (P0.05). Conclusion High glucose can promote the expression of A-FABP and the release of inflammatory factors by inducing the activation of TLR4/ phosphate JNK signaling pathway in THP-1 macrophages. Compared with the constant high glucose, volatile high glucose could further induce the activation of TLR4/ phosphorylated JNK signaling pathway, the expression of A-FABP and the secretion of inflammatory factors in THP-1 macrophages.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R363

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