【摘要】：目的探討高容量血液濾過(HVHF)對多臟器功能障礙綜合征(MODS)犬內(nèi)質(zhì)網(wǎng)應(yīng)激標(biāo)志蛋白JNK2 m RNA表達(dá)的影響。方法采用二次打擊建立犬MODS模型,12只犬隨機(jī)分為MODS組(n=6)和HVHF組(n=6),HVHF組給予HVHF治療24 h。于術(shù)前(T1),內(nèi)毒素注射完后0 h(T2)、6 h(T3)、12 h(T4)及24 h(T5)留取血標(biāo)本。體內(nèi)實(shí)驗(yàn):檢測肝、肺、腎組織細(xì)胞JNK2 m RNA水平。體外實(shí)驗(yàn):兩組血清體外誘導(dǎo)人臍靜脈內(nèi)皮細(xì)胞(HUVECs)建立內(nèi)質(zhì)網(wǎng)應(yīng)激凋亡模型。測定si RNA干擾前后JNK2 m RNA表達(dá)、蛋白表達(dá)及內(nèi)皮細(xì)胞凋亡率。結(jié)果體內(nèi)實(shí)驗(yàn):HVHF組肝臟JNK2 m RNA水平高于MODS組(P0.01)、肺臟明顯低于MODS組(P0.01)。體外實(shí)驗(yàn):(1)JNK2 m RNA表達(dá):與T1時(shí)間相比,HVHF組在T3~T5 JNK2 m RNA水平明顯降低,差異有統(tǒng)計(jì)學(xué)意義(P0.01);與si RNA干擾前相比,干擾后兩組JNK2 m RNA表達(dá)水平均明顯下降,差異具有統(tǒng)計(jì)學(xué)意義(P0.01);(2)JNK蛋白表達(dá):與T1時(shí)間相比,HVHF組在T3~T5JNK蛋白表達(dá)明顯降低,差異有統(tǒng)計(jì)學(xué)意義(P0.01);與MODS組相比,HVHF組在T3~T5 JNK蛋白表達(dá)明顯降低,差異有統(tǒng)計(jì)學(xué)意義(P0.01);與si RNA干擾前相比,干擾后兩組JNK蛋白表達(dá)均明顯下降,差異具有統(tǒng)計(jì)學(xué)意義(P0.01);(3)內(nèi)皮細(xì)胞凋亡率:與T1時(shí)間相比,HVHF組在T3~T5內(nèi)皮細(xì)胞凋亡率明顯降低,差異有統(tǒng)計(jì)學(xué)意義(P0.01);與MODS組相比,HVHF組在T3~T5內(nèi)皮細(xì)胞凋亡率明顯降低,差異有統(tǒng)計(jì)學(xué)意義(P0.01);與si RNA干擾前相比,干擾后兩組內(nèi)皮細(xì)胞凋亡率均明顯下降,差異具有統(tǒng)計(jì)學(xué)意義(P0.01)。結(jié)論 JNK信號通路介導(dǎo)了MODS犬過度內(nèi)質(zhì)網(wǎng)應(yīng)激時(shí)的細(xì)胞凋亡,HVHF可通過清除炎癥介質(zhì),減少氧化應(yīng)激,減輕內(nèi)質(zhì)網(wǎng)應(yīng)激,減少細(xì)胞凋亡。
[Abstract]:Aim to investigate the effect of high volume hemofiltration (HVHF) on the expression of endoplasmic reticulum stress marker JNK2 m RNA in dogs with multiple organ dysfunction syndrome (MODS). Methods 12 dogs were randomly divided into two groups: MODS group (n = 6) and HVHF group (n = 6), HVHF) treated with HVHF for 24 h. The MODS model of dogs was established by twice beating. Blood samples were collected before operation (T1), 0 h (T 2), 6 h (T 3), 12 h (T 4) and 24 h (T 5) after endotoxin injection. In vivo experiment: the levels of JNK2 m RNA in liver, lung and kidney were measured. In vitro experiment: two groups of serum induced human umbilical vein endothelial cell (HUVECs) in vitro to establish endoplasmic reticulum stress apoptosis model. The expression of JNK2 m RNA, the expression of protein and the apoptosis rate of endothelial cells were measured before and after si RNA interference. Results in vivo, the level of JNK2 m RNA in liver of HVHF group was higher than that of MODS group (P0.01), and the level of lung was significantly lower than that of MODS group (P0.01). In vitro experiment: (1) JNK2 m RNA expression: compared with T1 time, the level of T3~T5 JNK2 m RNA in HVHF group was significantly lower than that in T1 group (P0.01). Compared with that before si RNA interference, the expression level of JNK2 m RNA in the two groups was significantly decreased after the interference (P0.01). (2) the expression of JNK protein: compared with T1 time, the expression of T3~T5JNK protein in HVHF group was significantly lower than that in MODS group (P0.01), and the expression of T3~T5JNK protein in HVHF group was significantly lower than that in MODS group (P0.01). Compared with that before si RNA interference, the expression of JNK protein in the two groups decreased significantly after interference (P0.01). (3) apoptosis rate of endothelial cells: compared with T1 time, the apoptosis rate of T3~T5 in HVHF group was significantly lower than that in T1 group (P0.01). Compared with MODS group, the apoptosis rate of T3~T5 endothelial cells in HVHF group was significantly lower than that in T3~T5 group (P0.01). Compared with that before si RNA interference, the apoptosis rate of endothelial cells in the two groups decreased significantly after interference, the difference was statistically significant (P0.01). Conclusion JNK signaling pathway mediates apoptosis during excessive endoplasmic reticulum stress in MODS dogs. HVHF can eliminate inflammatory mediators, reduce oxidative stress, relieve endoplasmic reticulum stress and reduce apoptosis.
【作者單位】： 新疆醫(yī)科大學(xué)第一附屬醫(yī)院腎病科;霍城縣第一人民醫(yī)院內(nèi)科;
【基金】：新疆維吾爾自治區(qū)自然科學(xué)基金(2012211A065)
【分類號】：R459.7

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