本文選題：膿毒癥　切入點：急性肝損傷　出處：《山西醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:探討烏司他丁對脂多糖誘導(dǎo)的大鼠膿毒癥急性肝損傷的治療作用以及相關(guān)機制,并與炎癥通道阻斷劑的療效進行比較。方法:清潔級雄性SD大鼠32只,隨機分為4組,每組8只,分別為:空白組,脂多糖組,脂多糖+烏司他丁組,脂多糖+通道阻斷劑組。造模后24小時處死大鼠,取下腔靜脈血測定大鼠血清中谷丙轉(zhuǎn)氨酶、膽紅素和堿性磷酸酶的濃度,利用ELISA法測定大鼠肝組織腫瘤壞死因子-α水平,Western-blot法測定大鼠肝組織磷酸化p38蛋白水平表達,以及肝組織病理切片和電鏡切片觀察肝細胞微結(jié)構(gòu)的變化。結(jié)果:肝組織病理切片與空白組比較,LPS組存在明顯的肝細胞腫脹,肝細胞水樣變性,細胞間隙模糊不清,炎性細胞浸潤,肝細胞再生;LPS+UTI組和LPS+UTI組肝細胞腫脹、水樣變性、炎細胞浸潤及肝細胞再生均較LPS組減輕,但較空白組嚴重。肝組織電鏡片與空白組比較,LPS組肝細胞核固縮,細胞質(zhì)疏松,出現(xiàn)空泡變性或脂肪變性,線粒體體積明顯增大,外膜界限不清,線粒體嵴腫脹、斷裂甚至消失,內(nèi)質(zhì)網(wǎng)結(jié)構(gòu)不清。LPS+UTI組無明顯的肝細胞核固縮,線粒體體積稍增大,外膜界限清楚,線粒體嵴清楚,部分有斷裂,內(nèi)質(zhì)網(wǎng)結(jié)構(gòu)清楚。LPS+SB組肝細胞核固縮,線粒體稍腫脹,線粒體外膜界限清晰,但線粒體嵴模糊不清或者斷裂,內(nèi)質(zhì)網(wǎng)輪廓不清晰。與其他各組比較,LPS組肝臟組織TNF-α水平及磷酸化P38蛋白明顯升高(P0.05),差異具有統(tǒng)計學(xué)意義;空白組、LPS+UTI組以及LPS+SB組之間肝臟組織TNF-α水平無明顯差異(P0.05)。與空白組比較,LPS組血清ALT明顯升高(P0.001),LPS+UTI組血清ALT較LPS組降低(P0.05),但較空白組及LPS+SB組升高(P0.001),LPS+SB組與空白組之間無顯著性差異(P0.05)。四組血清AKP水平相比無顯著性差異(P0.05)。LPS組血清BIL較空白組明顯升高(P0.001),空白組與LPS+UTI組血清BIL相比、LPS組與LPS+SB組相比血清BIL無顯著性差異(P0.05)。結(jié)論:烏司他丁可以減輕脂多糖引起的大鼠膿毒癥急性肝損傷,使血清谷丙轉(zhuǎn)氨酶、膽紅素、肝組織腫瘤壞死因子-α水平降低,肝組織病理和電鏡結(jié)果提示炎癥反應(yīng)減輕,P38MAPK通路下游蛋白磷酸化p38蛋白水平降低,考慮烏司他丁是通過P38MAPK通路來發(fā)揮炎癥抑制作用的。與P38MAPK通路特異性阻斷劑比較,兩者減輕腫瘤壞死因子-α、磷酸化p38蛋白等炎癥因子和蛋白的作用是相似的,但是對血清學(xué)指標的影響及鏡下表現(xiàn)有一定差別。
[Abstract]:Objective: to investigate the therapeutic effect of ulinastatin on acute hepatic injury induced by lipopolysaccharide in rats and to compare the therapeutic effect with inflammatory channel blocker. Methods: Thirty-two clean male SD rats were randomly divided into 4 groups. Eight rats in each group were divided into blank group, lipopolysaccharide group, lipopolysaccharide ulinastatin group and lipopolysaccharide channel blocker group. The concentrations of bilirubin and alkaline phosphatase, the expression of phosphorylated p38 protein in rat liver tissue were determined by ELISA assay and Western-blot. Results: compared with the control group, lipopolysaccharide (LPS) group had obvious hepatocyte swelling, hepatocyte hydrophoretic degeneration and unclear cell space. Inflammatory cell infiltration, hepatocyte regeneration, hepatocyte swelling, water like degeneration, inflammatory cell infiltration and hepatocyte regeneration in lipopolysaccharide (UTI) group and LPS UTI group were less than those in LPS group, but more serious than those in blank group. The cytoplasm was loose, vacuolar degeneration or steatosis occurred, the volume of mitochondria increased obviously, the outer membrane boundary was unclear, the mitochondrial ridge was swollen, broken or even disappeared, and the endoplasmic reticulum structure was unclear. LPs UTI group had no obvious pyknosis of liver nucleus. The size of mitochondria was a little larger, the outer membrane boundary was clear, the mitochondrial ridge was clear, some of them were broken, the endoplasmic reticulum structure was clear. In LPS SB group, the nucleus of liver was constricted, the mitochondria was slightly swollen, and the outer membrane of mitochondria was clear, but the ridge of mitochondria was blurred or broken. Compared with other groups, the level of TNF- 偽 and phosphorylated P38 protein in lipopolysaccharide group increased significantly (P 0.05). There was no significant difference in the level of TNF- 偽 in liver tissue between UTI group and LPS SB group. Compared with the blank group, the serum level of TNF- 偽 in lipopolysaccharide group was significantly higher than that in the control group. Compared with the control group, the serum ALT level in the LPS UTI group was significantly lower than that in the LPS group, but it was higher than that in the blank group and LPS SB group. There was no significant difference in serum AKP level among the four groups. The serum BIL level in the four groups was significantly higher than that in the blank group (P 0.001). There was no significant difference in serum BIL between the LPS UTI group and the LPS UTI group compared with the LPS SB group. On: ulinastatin can alleviate acute liver injury induced by lipopolysaccharide in rats with sepsis. The levels of serum alanine aminotransferase, bilirubin, tumor necrosis factor- 偽 in liver tissue were decreased, and the pathological and electron microscopic results showed that inflammatory reaction reduced the level of phosphorylated p38 protein downstream of P38 MAPK pathway. It is considered that ulinastatin plays a role in inflammatory inhibition through the P38MAPK pathway. Compared with P38MAPK pathway specific blockers, both have similar effects on reducing inflammatory factors and proteins, such as tumor necrosis factor- 偽, phosphorylated p38 protein, and so on. However, there are some differences in the influence of serological indexes and the performance under microscope.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R459.7

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