Death following situations of intense emotional stress has been linked to the cardiac pathology described as stress cardiomyopathy, whose pathomechanism is still not clear. In this study, we sought to determine, via a...Death following situations of intense emotional stress has been linked to the cardiac pathology described as stress cardiomyopathy, whose pathomechanism is still not clear. In this study, we sought to determine, via an animal model, whether the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α) and the amino peptide neuropeptide Y (NPY) play a role in the pathogenesis of this cardiac entity. Male Sprague-Dawley rats in the experimental group were subjected to immobilization in a plexy glass box for 1 h, which was followed by low voltage elec-tric foot shock for about 1h at 10s intervals in a cage fitted with metallic rods. After 25 days the rats were sacrificed and sections of their hearts were processed. Hematoxylin-eosin staining of cardiac tissues revealed the characteristic cardiac lesions of stress cardiomyopathy such as contraction band necrosis, inflammatory cell infiltration and fibrosis. The semi-quantitative RT-PCR analysis for PGC-1α mRNA expression showed significant overexpression of PGC1-α in the stress-subjected rats (P<0.05). Fluorescence immunohistochemistry revealed a higher production of NPY in the stress-subjected rats as compared to the control rats (P=0.0027). Thus, we are led to conclude that following periods of intense stress, an increased expression of PGC1-α in the heart and an overflow of NPY may lead to stress car-diomyopathy and even death in susceptible victims. Moreover, these markers can be used to identify stress cardiomyopathy as the cause of sudden death in specific cases.展开更多
The present study aimed to explore the molecular mechanisms underlying the increase of nicotinamide adenine dinucleotide phosphate:quinine oxidoreductase 1(NQO1)and y-glutamylcysteine synthetase(γ-GCS)in brain tissue...The present study aimed to explore the molecular mechanisms underlying the increase of nicotinamide adenine dinucleotide phosphate:quinine oxidoreductase 1(NQO1)and y-glutamylcysteine synthetase(γ-GCS)in brain tissues after intracerebral hemorrhage(ICH).The microglial cells obtained from newborn rats were cultured and then randomly divided into the normal control group(NC group),model control group(MC group),rosiglitazone(RSG)intervention group(RSG group),retinoic-acid intervention group(RSG+RA group),and sulfbraphane group(RSG+SF group).The expression levels of NQO1,γ-GCS,and nuclear factor E2-related factor 2(Nrf2)were measured by real-time polymerase chain reaction(RT-PCR)and Western blotting,respectively.The results showed that the levels of NQO1,γ-GCS and Nrf2 were significantly increased in the MC group and the RSG group as compared with those in the NC group(P<0.01).They were found to be markedly decreased in the RSG+RA group and increased in the RSG+SF group when compared with those in the MC group or the RSG group(P<0.01).The RSG+SF group displayed the highest levels of NQO1,γ-GCS,and Nrf2 among the five groups.In conclusion,a medium dose of RSG increased the anti-oxidative ability of thrombinactivated microglia by increasing the expression of NQO1 and γ-GCS.The molecular mechanisms underlying the increase of NQO1 and γ-GCS in thrombin-activated microglia may be associated with the activation of Nrf2.展开更多
Patients undergoing Roux-en-Y gastric bypass(RYGB)surgery elicit striking loss of body weight. Anatomical restructuring of the gastrointestinal(GI) tract, leading to reduced caloric intake and changes in food preferen...Patients undergoing Roux-en-Y gastric bypass(RYGB)surgery elicit striking loss of body weight. Anatomical restructuring of the gastrointestinal(GI) tract, leading to reduced caloric intake and changes in food preference, are thought to be the primary drivers of weight loss in bariatric surgery patients. However, the mechanisms by which RYGB surgery causes a reduced preference for fatty foods remain elusive. In a recent report, Hankir et al described how RYGB surgery modulated lipid nutrient signals in the intestine of rats to blunt their craving for fatty food. The authors reported that RYGB surgery restored an endogenous fat-satiety signaling pathway, mediated via oleoylethanolamide(OEA), that was greatly blunted in obese animals. In RYGB rats, high fat diet(HFD) led to increased production of OEA that activated the intestinal peroxisome proliferation activator receptors-α(PPARα). In RYGB rats, activation of PPARα by OEA was accompanied by enhanced dopamine neurotransmission in the dorsal striatum and reduced preference for HFD. The authors showed that OEA-mediated signals to the midbrain were transmitted via the vagus nerve. Interfering with either the production of OEA in enterocytes, or blocking of vagal and striatal D1 receptors signals eliminated the decreased craving for fat in RYGB rats. These studies demonstrated that bariatric surgery led to alterations in the reward circuitry of the brain in RYGB rats and reduced their preference for HFD.展开更多
Background： In vitro experiments have revealed that toll-like receptor 4 （TLR4） pathway is involved in the progression ofimmunoglobulin A nephropathy （IgAN） by induction of proinflammatory cytokines. Evidence sho...Background： In vitro experiments have revealed that toll-like receptor 4 （TLR4） pathway is involved in the progression ofimmunoglobulin A nephropathy （IgAN） by induction of proinflammatory cytokines. Evidence showed that, in other disease models, peroxisome proliferator-activated receptor-7 （PPAR-7） agonists have been shown to exert anti-inflammatory effects through suppression of the expression and activity of TLR4. However, the interaction between PPAR-7 and TLR4 in IgAN has not been fully studied both in vitro and in vivo. In this study, we explored whether TLR4 pathway attributed to the progression of IgAN in experimental rats. Methods： Bovine gamma globulin was used to establish IgAN model. Fifty-four Lewis rats were randomly divided into six groups： ControliaK242, IgANTAK242, toll-like receptor 4 inhibitor （TAK242） groups （rats were administrated with TLR4 inhibitor, TAK242） and Controlpo, IgANpo, Pio groups （rats were administrated with PPAR-y agonist, pioglitazone）. Urinary albumin-to-creatinine ratio （ACR）, serum creatinine, and blood urea nitrogen were detected by automatic biochemical analyzer. Renal histopathological changes were observed after hematoxylin-eosin staining, and the IgA deposition in glomeruli was measured by immunofluorescence staining. Real-time polymerase chain reaction and Western blotting were used to detect TLR4 and interleukin- 1 beta （IL- 1β） message ribonucleic acid （mRNA） and protein expression in renal tissues. Results were presented as mean -4- standard deviation. Differences between groups were analyzed by one-way analysis of variance. Results： Compared to normal rats, experimental rats showed higher ACR （4.45 ± 1.33 mg/mmol vs. 2.89 ± 0.96 mg/mmol, P 〈 0.05）, obvious IgA deposition with mesangial hypercellularity, hyperplasia of mesangial matrix accompanied by increased serum IL-Iβ （48.28 ± 13.49 μg/ml vs. 35.56 ± 7.41μg/ml, P 〈 0.05）, and renal expression of IL-Iβ and TLR4. The biochemical parameters and renal pathological injury were relieved in both TAK242 group and Pio group. The expressions of renal tissue TLR4, IL-Iβ, and serum IL- 1 β were decreased in rats treated with TAK242, and the expression ofTLR4 mRNA and protein was significantly reduced in Pio group compared to IgANpo group （1.22 4± 0.28 vs. 1.72 ± 0.45, P 〈 0.01, and 0.12 ± 0.03 vs. 0.21 ± 0.05, P 〈 0.01）. Conclusions： Our study proves that inflammation mediated by TLR4 signaling pathway is involved in the progression of IgAN in rat models. Moreover, pioglitazone can inhibit the expression of TLR4 in IgAN.展开更多
基金supported by a grant from the National Natural Science Foundation of China(No.81172898)
文摘Death following situations of intense emotional stress has been linked to the cardiac pathology described as stress cardiomyopathy, whose pathomechanism is still not clear. In this study, we sought to determine, via an animal model, whether the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α) and the amino peptide neuropeptide Y (NPY) play a role in the pathogenesis of this cardiac entity. Male Sprague-Dawley rats in the experimental group were subjected to immobilization in a plexy glass box for 1 h, which was followed by low voltage elec-tric foot shock for about 1h at 10s intervals in a cage fitted with metallic rods. After 25 days the rats were sacrificed and sections of their hearts were processed. Hematoxylin-eosin staining of cardiac tissues revealed the characteristic cardiac lesions of stress cardiomyopathy such as contraction band necrosis, inflammatory cell infiltration and fibrosis. The semi-quantitative RT-PCR analysis for PGC-1α mRNA expression showed significant overexpression of PGC1-α in the stress-subjected rats (P<0.05). Fluorescence immunohistochemistry revealed a higher production of NPY in the stress-subjected rats as compared to the control rats (P=0.0027). Thus, we are led to conclude that following periods of intense stress, an increased expression of PGC1-α in the heart and an overflow of NPY may lead to stress car-diomyopathy and even death in susceptible victims. Moreover, these markers can be used to identify stress cardiomyopathy as the cause of sudden death in specific cases.
基金grants from the National Natural Science Foundation of China(No.81560222)the Guizhou Science and Technology Foundation(No.[2017]7187,and No.[2013]2043).
文摘The present study aimed to explore the molecular mechanisms underlying the increase of nicotinamide adenine dinucleotide phosphate:quinine oxidoreductase 1(NQO1)and y-glutamylcysteine synthetase(γ-GCS)in brain tissues after intracerebral hemorrhage(ICH).The microglial cells obtained from newborn rats were cultured and then randomly divided into the normal control group(NC group),model control group(MC group),rosiglitazone(RSG)intervention group(RSG group),retinoic-acid intervention group(RSG+RA group),and sulfbraphane group(RSG+SF group).The expression levels of NQO1,γ-GCS,and nuclear factor E2-related factor 2(Nrf2)were measured by real-time polymerase chain reaction(RT-PCR)and Western blotting,respectively.The results showed that the levels of NQO1,γ-GCS and Nrf2 were significantly increased in the MC group and the RSG group as compared with those in the NC group(P<0.01).They were found to be markedly decreased in the RSG+RA group and increased in the RSG+SF group when compared with those in the MC group or the RSG group(P<0.01).The RSG+SF group displayed the highest levels of NQO1,γ-GCS,and Nrf2 among the five groups.In conclusion,a medium dose of RSG increased the anti-oxidative ability of thrombinactivated microglia by increasing the expression of NQO1 and γ-GCS.The molecular mechanisms underlying the increase of NQO1 and γ-GCS in thrombin-activated microglia may be associated with the activation of Nrf2.
文摘Patients undergoing Roux-en-Y gastric bypass(RYGB)surgery elicit striking loss of body weight. Anatomical restructuring of the gastrointestinal(GI) tract, leading to reduced caloric intake and changes in food preference, are thought to be the primary drivers of weight loss in bariatric surgery patients. However, the mechanisms by which RYGB surgery causes a reduced preference for fatty foods remain elusive. In a recent report, Hankir et al described how RYGB surgery modulated lipid nutrient signals in the intestine of rats to blunt their craving for fatty food. The authors reported that RYGB surgery restored an endogenous fat-satiety signaling pathway, mediated via oleoylethanolamide(OEA), that was greatly blunted in obese animals. In RYGB rats, high fat diet(HFD) led to increased production of OEA that activated the intestinal peroxisome proliferation activator receptors-α(PPARα). In RYGB rats, activation of PPARα by OEA was accompanied by enhanced dopamine neurotransmission in the dorsal striatum and reduced preference for HFD. The authors showed that OEA-mediated signals to the midbrain were transmitted via the vagus nerve. Interfering with either the production of OEA in enterocytes, or blocking of vagal and striatal D1 receptors signals eliminated the decreased craving for fat in RYGB rats. These studies demonstrated that bariatric surgery led to alterations in the reward circuitry of the brain in RYGB rats and reduced their preference for HFD.
文摘目的观察厄贝沙坦联合瑞舒伐他汀对血管损伤小鼠血管重构的影响。方法 8周龄C57BL/6野生型雄性小鼠50只,随机分成5组:假手术组、手术组、厄贝沙坦治疗组(50 mg/kg·d)、瑞舒伐他汀治疗组(5 mg/kg·d)、厄贝沙坦(0.5 mg/kg·d)联合瑞舒伐他汀治疗组(2 mg/kg·d),每组10只。手术使用套管制作股动脉损伤模型。连续灌胃给药14 d后处死小鼠。留取小鼠股动脉标本,分别采用HE染色及NIH图像分析软件测量血管内膜面积,RT-PCR法检测MCP-1、CCR2及PPARγm RNA表达水平。各组小鼠检测实验前后血脂及肝功能指标。结果假手术组(0μm2)未见血管内膜增生。新生内膜面积手术组(6497±5.7)μm2、厄贝沙坦治疗组(5979±1.4)μm2、瑞舒伐他汀治疗组(6005±5.8)μm2、厄贝沙坦联合瑞舒伐他汀治疗组(2269±2.8)μm2,均有新生内膜形成,与假手术组比较有统计学差异(P均<0.05)。与手术组比较,厄贝沙坦治疗组、瑞舒伐他汀治疗组新生内膜面积差异无统计学意义(P均>0.05)。与手术组、厄贝沙坦治疗组、瑞舒伐他汀治疗组比较,厄贝沙坦联合瑞舒伐他汀治疗组内膜增生面积降低,差异有统计学意义(P均<0.05)。MCP-1 m RNA相对表达量:与假手术组比较,手术组、厄贝沙坦治疗组、瑞舒伐他汀治疗组、厄贝沙坦联合瑞舒伐他汀治疗组相对表达量增加,差异有统计学意义(P均<0.05)。与手术组、厄贝沙坦治疗组、瑞舒伐他汀治疗组比较,厄贝沙坦联合瑞舒伐他汀治疗组相对表达量降低,差异有统计学意义(P均<0.05)。CCR2 m RNA相对表达量:与假手术组比较,手术组、厄贝沙坦治疗组、瑞舒伐他汀治疗组、厄贝沙坦联合瑞舒伐他汀治疗组增加,差异有统计学意义(P均<0.05)。PPARγm RNA相对表达量:与假手术组比较,手术组、厄贝沙坦治疗组、瑞舒伐他汀治疗组、厄贝沙坦联合瑞舒伐他汀治疗组相对表达量降低,差异有统计学意义(P均<0.05)。与手术组、厄贝沙坦治疗组、瑞舒伐他汀治疗组比较,厄贝沙坦联合瑞舒伐他汀治疗组相对表达量增加,差异有统计学意义(P均<0.05)。MCP-1 m RNA相对表达量与PPARγ相对表达量呈负相关(r=-0.607,P<0.05)。结论厄贝沙坦联合瑞舒伐他汀可能通过增加PPARγ表达,降低MCP-1表达,延缓损伤血管的重构。
文摘Background： In vitro experiments have revealed that toll-like receptor 4 （TLR4） pathway is involved in the progression ofimmunoglobulin A nephropathy （IgAN） by induction of proinflammatory cytokines. Evidence showed that, in other disease models, peroxisome proliferator-activated receptor-7 （PPAR-7） agonists have been shown to exert anti-inflammatory effects through suppression of the expression and activity of TLR4. However, the interaction between PPAR-7 and TLR4 in IgAN has not been fully studied both in vitro and in vivo. In this study, we explored whether TLR4 pathway attributed to the progression of IgAN in experimental rats. Methods： Bovine gamma globulin was used to establish IgAN model. Fifty-four Lewis rats were randomly divided into six groups： ControliaK242, IgANTAK242, toll-like receptor 4 inhibitor （TAK242） groups （rats were administrated with TLR4 inhibitor, TAK242） and Controlpo, IgANpo, Pio groups （rats were administrated with PPAR-y agonist, pioglitazone）. Urinary albumin-to-creatinine ratio （ACR）, serum creatinine, and blood urea nitrogen were detected by automatic biochemical analyzer. Renal histopathological changes were observed after hematoxylin-eosin staining, and the IgA deposition in glomeruli was measured by immunofluorescence staining. Real-time polymerase chain reaction and Western blotting were used to detect TLR4 and interleukin- 1 beta （IL- 1β） message ribonucleic acid （mRNA） and protein expression in renal tissues. Results were presented as mean -4- standard deviation. Differences between groups were analyzed by one-way analysis of variance. Results： Compared to normal rats, experimental rats showed higher ACR （4.45 ± 1.33 mg/mmol vs. 2.89 ± 0.96 mg/mmol, P 〈 0.05）, obvious IgA deposition with mesangial hypercellularity, hyperplasia of mesangial matrix accompanied by increased serum IL-Iβ （48.28 ± 13.49 μg/ml vs. 35.56 ± 7.41μg/ml, P 〈 0.05）, and renal expression of IL-Iβ and TLR4. The biochemical parameters and renal pathological injury were relieved in both TAK242 group and Pio group. The expressions of renal tissue TLR4, IL-Iβ, and serum IL- 1 β were decreased in rats treated with TAK242, and the expression ofTLR4 mRNA and protein was significantly reduced in Pio group compared to IgANpo group （1.22 4± 0.28 vs. 1.72 ± 0.45, P 〈 0.01, and 0.12 ± 0.03 vs. 0.21 ± 0.05, P 〈 0.01）. Conclusions： Our study proves that inflammation mediated by TLR4 signaling pathway is involved in the progression of IgAN in rat models. Moreover, pioglitazone can inhibit the expression of TLR4 in IgAN.
