C57BL/6小鼠胆结石形成中固醇载体蛋白2的mRNA水平和胆固醇饱和指数增高

目的观察C57BL/6鼠胆囊结石形成过程中肝固醇载体蛋白2(SCP2)mRNA水平及胆囊胆汁中胆固醇饱和指数的变化。方法C57BL/6鼠20只,分为结石组和对照组。对照组喂普通饲料,结石组采用1%的胆固醇饮食4周;RT-PCR方法检测肝SCP2 mRNA水平的变化;全自动生化仪检测胆脂,并计算胆固醇饱和指数。结果胆囊结石组肝SCP2 mRNA水平显著升高,胆汁胆固醇饱和指数亦显著增加。结论肝SCP2的表达及胆汁CSI的增高呈正相关。     

Effect of sex and exercise on liver and plasma lipids of the rat

The effect of voluntary exercise on plasma and hepatic lipids was studied in 24 week old male and female Long-Evans rats who were fed a high sucrose (73% of calories) diet containing saturated fat and cholesterol for a 10 week period. Blood lipids were analyzed at week 0, 2, 5 and 10 and liver lipids at week 0 and 10. Half of the animals were housed in individual activity wheels where the females voluntarily ran 4.3 miles/day and the males voluntarily ran 2.4 miles/day. Compared to the males, the females 1. exhibited a greater lipogenic response to the diet, 2. showed a greater lowering of plasma and liver triglyceride and plasma cholesterol ester with exercise, and 3. developed with exercise a higher relative heart weight. Exercise was successful in the males in producing a 75% reduction in the level of hepatic cholesterol ester seen in the non-exercising males. The importance of this study is seen in the lipid-lowering effects of voluntary exercise which avoids food and water deprivation and thus the stress concurrent with forced exercise regimes.     

Modulation of plasma lipid levels affects benzo[a]pyrene-induced DNA damage in tissues of two hyperlipidemic mouse models

The role of plasma lipids in the uptake, transportation, and distribution of lipophilic carcinogens like benzo[a]pyrene (B[a]P) remains unclear. Therefore, we studied the effects of dietary-modulated plasma lipids on B[a]P-induced DNA damage in several organs of two hyperlipidemic mouse models. Male apolipoprotein E (ApoE)*3-Leiden (n = 22) and ApoE knockout (ApoE-KO) mice (n = 20) were fed a high-fat cholesterol (HFC) diet or low-fat cholesterol (LFC; standard mouse chow) diet for 3 weeks, after which the animals were exposed to a single oral dose of 5 mg/kg bw B[a]P or vehicle and killed 4 days later. Plasma lipids were determined and DNA adducts were measured in aorta, heart, lung, liver, brain, and stomach. Total cholesterol and low-density lipoprotein (LDL) cholesterol were increased in all animals on a HFC diet, whereas a decrease of triglycerides was seen only in the ApoE-KO mice. In ApoE-KO mice on a normal diet, DNA-adduct levels were highest in aorta (10.8 +/- 1.4 adducts/10(8) nucleotides), followed by brain (7.8 +/- 1.3), lung (3.3 +/- 0.7), heart (3.1 +/- 0.6), liver (1.5 +/- 0.2) and stomach (1.2 +/- 0.2). In the ApoE*3-Leiden mice, adduct levels were equally high in aorta, heart, and lung (4.6 +/- 0.7, 5.0 +/- 0.5 and 4.6 +/- 0.4, respectively), followed by stomach (2.7 +/- 0.4), brain (2.3 +/- 0.2), and liver (1.7 +/- 0.2). In the ApoE-KO mice, the HFC diet intervention resulted in lower adduct levels in lung (2.1 +/- 0.2), heart (1.9 +/- 0.2), and brain (2.9 +/- 0.5), as compared with the LFC group. In contrast, a nonsignificant increase of adducts was found in aorta (13.1 +/- 1.5). A similar but nonsignificant trend was observed in the ApoE*3-Leiden mice. Multiple regression analysis showed that in aorta, DNA adducts were inversely related to plasma triglycerides (P = 0.004) and were also modulated by the ApoE genotype (P < 0.001). The results of the present study support further investigation into the role of dietary modulation of plasma lipids, ApoE, and polycyclic aromatic hydrocarbon exposure on the formation of DNA adducts in chronic degenerative diseases.     

The impact of psychogenic stressors on oxidative stress markers and patterns of CYP2E1 expression in mice liver

The increasing number of psychogenic stressors is a side effect of civilization. It results in the development of psychoemotional stresses and psychosomatic diseases. In this study we evaluated the effect of the chronic psychoemotional stress on the level of CYP2E1 expression in the liver of C57Bl/6 mice. Stress was induced by the immobilization of animals for 4h per day during 7 or 14 days. CYP2E1 expression level was evaluated on the 7th and 14th days of the experiment, respectively. We detected a twofold reduction in CYP2E1 protein expression level relatively to controls for both time points tested. This reduction was no longer significant when the effect of the stressor factor was terminated on the 14th day of the experiment and animals were analyzed one week later. Remarkably Cyp2e1 mRNA expression level was constant at any time point of the experiment. We also documented significant changes in the expression/activity of two oxidative stress markers examined in the liver of treated mice. The catalase activity decreased fivefold while malondialdehyde transiently increased threefold. These data suggest that oxidative stress can be involved in the reduction of hepatic CYP2E1 and catalase activity under the conditions of chronic emotional stress.     

Plasma triglycerides are not related to tissue lipids and insulin sensitivity in elderly following PPAR-alpha agonist treatment

Increases in plasma lipids, tissue triglycerides and decreases in mitochondrial function have been linked to insulin resistance and aging. In animals, peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonists decrease plasma lipids, intramyocellular fat (IMCL) and liver fat (LFAT) and improve mitochondrial beta-oxidative function and insulin sensitivity, but the effects in elderly were not known. Insulin sensitivity was assessed with a 2-h oral glucose tolerance test, magnetic resonance spectroscopy was used to asses IMCL, LFAT and plasma lipids were measured before and after 6, 11 and 61 days of PPAR-alpha agonist (fenofibrate) administration in 19 elderly (age 70+/-1 years) volunteers. Volunteers were stratified into healthy (N=7) and insulin resistant (N=12) groups. The baseline insulin sensitivity index (8.1+/-1.2 vs. 3.8+/-0.5, healthy vs. insulin resistant; P<0.001) was significantly higher in the healthy group. Fenofibrate treatment induced significant reductions in plasma triglycerides (P<0.001) and total cholesterol (P<0.001) in both groups. Nonetheless, neither fasted free fatty acids, glucose, insulin, nor insulin sensitivity improved in either group (day 1 vs. day 61, 8.1+/-1.2 vs. 8.1+/-0.9, healthy; and 3.8+/-0.5 vs. 4.2+/-0.05, insulin resistant). Furthermore, there was no change in IMCL or LFAT. These results indicate that whereas fenofibrate significantly lowers plasma lipids it neither affects insulin sensitivity nor intracellular lipids in elderly.     

Studies on the polyisoprenoid composition in hepatocellular carcinomas and its correlation with their differentiation

The levels of cholesterol, ubiquinone and dolichol and the polyprenol composition of dolichol in human hepatocellular carcinomas (hepatomas) with different degrees of differentiation were analyzed and compared with healthy liver tissue. Dolichols were also analyzed in liver metastases. The total level of cholesterol was increased, while the levels of dolichol and ubiquinone were decreased in all hepatomas, but no correlation between these levels and the degree of differentiation of the hepatomas could be observed. The level of dolichol decreased more in the hepatomas than in the liver metastases. The dolichol fraction from hepatomas with a low degree of differentiation contained higher relative amounts of short polyisoprenols (D17) and slightly lower relative amounts of D21 compared with healthy liver tissue, metastatic liver tumors or hepatomas with a high degree of differentiation. The significance of the lipid values found in the different groups is discussed.     

Differential effect of gamma-radiation-induced heme oxygenase-1 activity in female and male C57BL/6 mice

Ionizing radiation produces reactive oxygen species, which exert diverse biological effects on cells and animals. We investigated alterations of heme oxygenase (HO) and non-protein thiols (NPSH), which are known as two major anti-oxidant enzymes, in female and male C57BL/6 mice in the lung, liver, and brain after whole-body gamma-irradiation with 10 Gy (1-7 days) as well as in the lung after whole-thorax gamma-irradiation (WTI) with 12.5 Gy (1-26 weeks). Most significant alteration of HO activity was observed in the liver, which elevated 250% in males. NPSH level in female liver was increased on the 5th-7th days but decreased in males on the 3rd day. In the lung, the elevation of HO activity in both sexes and the pattern of NPSH change were similar to that of the liver. On the other hand, the increase of HO activity on the 16th week and the decrease of NPSH level on the 2nd week were observed only in male lung after WTI. This study shows that the liver is the most sensitive tissue to gamma-irradiation-induced alterations of HO activity in both female and male mice. In addition, there exists significant differential effect of gamma-irradiation on anti-oxidant system in female and male mice.     

不同进食量对小鼠功能活动和生化指标的影响

目的:探讨不同进食量在不同时间内对小鼠体重、记忆力、平衡耐力和相应生化指标的影响。方法:预先计算小鼠每天平均进食量,按照100%食量,75％食量、50％食量、25％食量及0％食量分为A、B、C、D、E组。实验过程中每3d测试记忆力、平衡耐力和体重1次,第10d取血检测相应生化指标。结果:实验第3d,E组体重、平衡耐力下降;实验第6d和第9d,A组、B组、C组体重明显上升,A组、D组动物的记忆力低于B组和C组;实验第10d,D组血糖显著下降,总胆固醇及甘油三酯随进食量的减少而显著下降。结论:适度减少进食量能维持正常体力和血糖水平,保持良好的记忆力,并有助于降低血中总胆固醇和甘油三酯。     

Effects of dietary cholesterol and voluntary exercise on histopathology,plasma and hepatic lipids of the male rat

Summary To avoid the stress of imposed activity, male weanling rats were allowed to exercise voluntarily in individual activity wheels. The exercising animals, which were compared to sedentary controls, ran over 26 km/wk (over 2 miles/day). Half of the animals in each group were fed a 10% coconut oil diet; the other half were fed the same diet with 1% added cholesterol.Plasma cholesterol was monitored throughout the 23-week regime. Consistently lower plasma cholesterol values were shown by the exercising animals during the first weeks of the study, the differences being statistically significant at the end of the 8th week. Dietary cholesterol sharply elevated plasma cholesterol, which reached a peak at the 5th week, then declined to basal levels by the 10th week.Both neutral glycerides and cholesterol levels of the livers were elevated considerably by the addition of cholesterol to the diet. Exercising, however, had a lowering effect on both liver cholesterol and neutral glycerides. The weights of the hearts of the exercising rats were increased, while those of the other organs selected were unchanged.Histologic examination of sections of livers showed fat infiltration of hepatic cells varying in severity, depending on the diet. Greater damage to liver cells was noted when cholesterol was added to the basal diet. Fat infiltration was lessened considerably in exercising rats on the basal diet; exercising partially overcame the effects of added cholesterol.This work was supported in part by Grant-In-Aid from The Nutrition Foundation, Inc.; State of Washington Initiative 171 Fund and USPHS Research Grant HD-03475 from the National Institutes of Health.     

小鼠皮下感染着色芽生菌病皮损中局部细胞免疫功能研究

目的 利用小鼠皮下着色芽生菌病模型,研究在不同的病程发展阶段其T细胞免疫功能的变化.方法 足垫局部皮下注射法建立小鼠的裴氏着色霉感染的着色芽生菌病模型,通过免疫组织化学技术,检测正常小鼠足垫皮肤皮损局部细胞因子IFN-γ、IL-4、IL-10、TNF-α的表达并作为对照组,观察免疫正常组和环磷酰胺免疫抑制处理的免疫抑制组小鼠分别在感染上述真菌后7 d、30 d时,皮损局部细胞因子水平变化,并与对照组比较.结果 在着色芽生菌病小鼠模型中,第7天时,免疫正常组IL-4、TNF-α和IL-10较正常对照组均出现了显著的升高(P＜0.01),表现为Th1和Th2型细胞免疫均增强的模式,并以Th2型为主;30 d时IL-10表达显著下降(P＜0.01),与同期正常对照组比较差异无统计学意义(P=0.52),IFN-γ、TNF-α水平比7 d时显著升高(P＜0.01),表现为Th2型细胞免疫减弱Th1型占主导的模式.免疫功能受损组第7天时IL-10、IL-4的水平升高与其他两组相比差异均有统计学意义(P＜0.01),IFN-γ表达水平则明显下降(P＜0.01),TNF-α的表达与正常对照组相比差异无统计学意义(P=0.39),表现为Th2型细胞免疫增强Th1功能受抑模式;30 d时,IL-10表达水平较7 d时显著减少,但仍然高于同期的免疫正常组和正常对照组,IFN-γ、TNF-α水平显著升高(P＜0.01),但却低于免疫正常组,表现为Th2型免疫模式渐弱Th1功能逐渐增强模式.结论 在不同免疫状态下小鼠着色芽生菌病感染的过程中,随着病情好转存在由Th2型细胞免疫为主导转化为Th1型细胞免疫功能占主导的过程,免疫抑制下主要表现为Th1反应受抑制,Th1型细胞因子在控制着色芽生菌病的发展过程中具有关键性的保护作用,Th2型细胞因子则可能与感染的发展进程相关.     

Fatty acid profile of plasma and liver lipids in mice depleted in long-chain polyunsaturated (n-3) fatty acids

Considering the numerous features of the metabolic syndrome found in rats depleted in long-chain polyunsaturated (n-3) fatty acids and in the perspective of further work conducted in (n-3)-depleted mice, the fatty acid profile of plasma and liver lipids was assessed in both male and female control and second-generation (n-3)-depleted mice. In addition to gender differences, the major alteration found in the (n-3)-depleted animals consisted in the expected severe depletion of plasma triacylglycerols and phospholipids, as well as liver phospholipids, in C20:5(n-3), C22:5(n-3) and C22:6(n-3). In plasma triacylglycerols, the weight percentages of C18:2(n-6) and C18:3(n-6) were lower in (n-3)-depleted mice than in control animals. In both plasma and liver phospholipids, however, the weight percentages of long-chain polyunsaturated (n-6) fatty acids (C20:4(n-6) and C22:4(n-6)) were higher in (n-3)-depleted mice than in control animals. The C16:1(n-7)/C16:0 and C18:1(n-9)/C18:0 ratio in both plasma and liver phospholipids were also increased in female (n-3)-depleted mice but not so in male animals. Highly significant correlations were found between the weight percentage of each fatty acid in liver versus plasma phospholipids. Taken as a whole, these findings indicate that second-generation mice depleted in (n-3) fatty acids represent a suitable model, in terms of the remodelling of the fatty acid profile in plasma and liver lipids, to investigate the metabolic and functional consequences of such a depletion.     

Carbon tetrachloride-induced hepatic fibrosis and cirrhosis in the developing rat: an experimental model of cirrhosis in childhood.

An experimental animal model designed specifically to simulate liver fibrosis and cirrhosis in childhood is described. Phenobarbitone was administered continuously from the 4th day of life and carbon tetrachloride intermittently from the 13th day to developing rats for 10 weeks. Treated animals showed hepatic necrosis, hepatic regeneration and a progressive increase in hepatic fibrosis; cirrhosis developed before the animals reached sexual maturity at 72 days or were fully grown. Hepatic prolyl hydroxylase activity increased to a maximum level after 20 days of treatment, before increased hepatic collagen could be detected, and fell to a lower level as cirrhosis became established. Serum activities of alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase gave a similar pattern, a marked increase at 20 days of age followed by a fall to near normal levels as hepatic damage became more severe. By the 26th day of life hepatic collagen levels were increased significantly and rose thereafter progressively as fibrosis became more widespread throughout the liver. Cirrhosis developed between the 38th and 75th days. Cirrhosis remained 10 weeks after discontinuation of treatment with phenobarbitone and carbon tetrachloride treatment.     

Carbon tetrachloride-induced hepatic fibrosis and cirrhosis in the developing rat: an experimental model of cirrhosis in childhood

An experimental animal model designed specifically to simulate liver fibrosis and cirrhosis in childhood is described. Phenobarbitone was administered continuously from the 4th day of life and carbon tetrachloride intermittently from the 13th day to developing rats for 10 weeks. Treated animals showed hepatic necrosis, hepatic regeneration and a progressive increase in hepatic fibrosis; cirrhosis developed before the animals reached sexual maturity at 72 days or were fully grown. Hepatic prolyl hydroxylase activity increased to a maximum level after 20 days of treatment, before increased hepatic collagen could be detected, and fell to a lower level as cirrhosis became established. Serum activities of alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase gave a similar pattern, a marked increase at 20 days of age followed by a fall to near normal levels as hepatic damage became more severe. By the 26th day of life hepatic collagen levels were increased significantly and rose thereafter progressively as fibrosis became more widespread throughout the liver. Cirrhosis developed between the 38th and 75th days. Cirrhosis remained 10 weeks after discontinuation of treatment with phenobarbitone and carbon tetrachloride treatment.     

Increased Hepatic Cholesterol Accumulation in Transgenic Mice Overexpressing Human Secretory Phospholipase A2 Group IIA

It has been demonstrated in transgenic mice that the overexpression of human phospholipase A2 group IIA (sPLA2), an acute-phase reactant, is associated with depressed plasma cholesterol levels, altered lipoprotein compositions, and increased lipid depositions in aortic walls. It was the aim of the present study to investigate whether the reduced plasma cholesterol levels in sPLA2-transgenic mice may be due to an increased transfer of lipids from sPLA2-modified lipoproteins to the liver and/or other nonvascular tissues. Ten sPLA2-transgenic mice and an equal number of nontransgenic littermates were fed a cholesterol-enriched (1%) diet for 13 weeks. After autopsy, cholesterol and triglyceride concentrations were measured in homogenates of liver, spleen, kidney, and myocardial tissues. Compared to the nontransgenic controls, the sPLA2-transgenic mice exhibited significantly lower plasma cholesterol levels, which was due to a reduction in both HDL and beta-lipoprotein (LDL + beta-VLDL) cholesterol. Liver tissues from the transgenic mice were found to contain significantly increased concentrations of free and esterified cholesterol, which was not associated with increased triglyceride concentrations. Spleen, kidney, and heart tissues of the two animal groups showed no significant differences in cholesterol or triglyceride concentrations. The findings suggest that the overexpression of human secretory phospholipase A2 group IIA leads to an enhanced delivery of cholesterol from phospholipolysed lipoproteins to the liver. This mechanism is likely to contribute to the development of hypocholesterolemia observed in patients with inflammatory diseases.     

Leukemia and cysts in mice of the AFB line

Summary Culture fluid from the 7th successive passage of human leukemic material through monkey kidney culture was injected into 6 mice of the high-leukemic strain Afb during the first day after birth. All the mice died between the 80th and 148th days after injection with systemic enlargement of the lymph glands. Serous and hemorrhagyc cysts were observed in 2 mice. Material from one of these mice sacrificed on the 125th day after birth was serially passaged through mice of the same strain. All of them developed leukemia. The leukemic line isolated, which was called Gamaleya No. 1, is hemocytoblastic in type. It is characterized by the absence of local tumor growth and by transplantability to mice of the low leukemic strain C3HA. The possible role of various factors in the development of early leukemia and casts in Afb mice is discussed.(Presented by Active Member of the Akad. Med. Nauk SSSR N. N. Zhukov-Verezhnikov) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 53, No. 1, pp. 86–92, January, 1962     

抑制NOX缓解酒精肝模型小鼠肝细胞损伤及脂代谢紊乱

背景:研究表明,应激状态下小鼠心肌、骨骼肌、肾脏及脑组织NOX蛋白过度上调,而NOX介导氧化应激在过量饮酒导致的酒精性肝损伤中的作用尚不清楚.目的:探讨NOX介导氧化应激在肝脏正常生理及酒精性肝损伤病理状态下的作用.方法:①6只雄性C57BL/6J小鼠随机分为正常对照组、正常药物组,每组3只;正常药物组腹腔注射NOX抑...     

Clinical significance of abnormal lipoprotein patterns in liver diseases

We analyzed lipids in liver diseases by agarose gel electrophoresis, and differential staining and simultaneous analysis of the cholesterol (Chol) and triglyceride (TG) fractions. Liver diseases were classified into chronic hepatitis (CH), liver cirrhosis (LC), hepatocellular carcinoma (HCC), and metastatic liver cancer, and each fraction was compared among these diseases. Atypical patterns that were unclassifiable according to the WHO classification of hyperlipidemia phenotypes were classified, and their clinical importance was evaluated. With progression of the pathologic conditions of CH, LC, and HCC, the T-Chol level, each Chol fraction, and the TG fraction decreased while the LDL-TG fraction increased. Metastatic liver cancer showed a lower HDL-fraction level but higher levels of the other parameters than HCC. When the subjects were classified into survivors and patients who died, the HDL fraction level in HCC and metastatic liver cancer, and the LDL level in LC and metastatic liver cancer differed between survivors and patients who died. Phenotypes of hyperlipidemia also differed among diseases, and atypical patterns were frequently observed in patients who died. There were 6 atypical patterns, of which 4 (slow alpha HDL, abnormal LDL, Lp-X, and Lp-Y) were associated with liver diseases. Slow alpha HDL appeared during slight bile stagnation and was accompanied by increases in the apo E level and the HDL particle size. Abnormal LDL appeared with severe liver dysfunction; a TG peak appeared at the position of LDL, and the HDL and VLDL fractions were negligible. Lp-X was a Chol-rich band, occurring on the cathode side of LDL in the presence of marked bile stagnation such as that in obstructive jaundice, and was accompanied by appearance of abnormal LDL. Lp-Y was similar to Lp-X in terms of mobility and associated diseases but contained Chol and TG. Abnormal LDL, Lp-X, and Lp-Y were often observed in patients with poor outcomes. Lipid analysis in liver diseases by this method showed results reflecting the pathologic conditions and may be clinically useful.     

Liver injury and viremia in mice infected with dengue-2 virus

The goal of this study was to test the feasibility of BALB/c mice as an experimental model in the study of dengue disease. BALB/c mice were intraperitoneal infected with DENV-2 obtained from a human patient. Histopathological analysis of infected animals revealed liver injury with viral antigens detection. In initial stages, the most prominent lesions were vacuolization and diffuse steatosis in hepatocytes. Serum levels of ALT and AST increased progressively, reaching the highest values 7 days p.i. and decreasing at the 14th day. Since levels of circulating virus were very low, viremia was analyzed in C6/36 cells. Virus presence was detected by ultrastructural analysis, confirmed by RT-PCR assays. Period of viremia was analyzed by flow cytometry with cells incubated with mouse-infected sera collected in different days, revealing peak virus levels at the 7th day p.i. All such data correlate to the development of the disease described in humans.     

芥子碱硫氰酸盐抑制IR小鼠血脂血糖升高、动脉粥样硬化及肝细胞脂肪变性

目的:探究芥子碱硫氰酸盐(sinapine thiocyanate,ST)抑制胰岛素抵抗(insulin resistance,IR)小鼠血脂血糖升高、动脉粥样硬化及肝细胞脂肪变性的机制。方法:Apo E~(-/-)雄性小鼠60只随机分成对照组、生理盐水组、罗格列酮组和ST低、中、高剂量治疗组,每组10只。除对照组常规饲料喂养外,其余各组以高脂饲料饲养12周,ST低、中、高剂量组同时给予ST(10、30和90 mg·kg~(-1)·d~(-1))灌胃,罗格列酮组给予罗格列酮(1.33 mg·kg~(-1)·d~(-1))灌胃。最后3周,除对照组腹腔注射生理盐水外,其余各组腹腔注射地塞米松(0.8 mg·kg~(-1)·d~(-1))诱导IR。每周断尾采血检测空腹血糖水平,第12周末禁食12 h后处死动物取样,检测空腹胰岛素、肿瘤坏死因子α(TNF-α)、甘油三酯、总胆固醇及肝脂质等水平;将肝组织和主动脉固定包埋切片,HE染色。Western blot测定肝脂质代谢与骨骼肌MAPK信号通路相关蛋白表达。结果:ST呈剂量依赖性降低血脂、血糖及TNF-α等代谢相关指标的水平(P0.05),延缓肝细胞脂肪变性和动脉粥样硬化;并呈剂量依赖性调控肝脂质代谢信号通路(HMGR和SREBP-2等)及MAPK信号通路(ERK和p38等)蛋白表达(P0.05)。结论:ST抑制IR模型小鼠血脂血糖升高、动脉粥样硬化及肝细胞脂肪变性的机制可能与调控肝脂质代谢和骨骼肌MAPK信号通路相关蛋白表达有关。     

NLRP3炎症小体介导的炎症反应参与糖尿病导致的肾损伤和脂代谢异常

目的:观察NLRP3在糖尿病肾组织炎症及胆固醇代谢中的作用及机制。方法:实验小鼠分为4组:对照(WT)组、糖尿病(WT+STZ)组、NLRP3基因敲除(NKO)组和NLRP3基因敲除+糖尿病(NKO+STZ)组。腹腔注射STZ构建糖尿病小鼠模型。观察小鼠血尿生化指标及肾组织形态学;电镜及油红O染色观察肾组织脂滴形成情况;Western blot方法检测NLRP3、ASC、caspase-1、IL-1β、IL-18及胆固醇代谢指标SCAP、SREBP-2、HMGCR、LDLR、LXRα和ABCA1的蛋白表达情况及p38 MAPK的磷酸化情况。结果:与WT组小鼠相比,糖尿病小鼠肾组织的NLRP3表达和p38 MAPK的磷酸化水平显著升高;肾组织内炎症明显,胆固醇含量增加伴肾功能受损;敲除NLRP3显著减轻糖尿病小鼠肾组织炎症反应及胆固醇沉积,同时抑制p38 MAPK的磷酸化。结论:NLRP3介导的炎症反应在糖尿病肾损伤及脂代谢异常中发挥重要作用,这种作用可能与p38 MAPK信号通路的活化密切相关。