Effect of HJJB Compound on Insulin Signal Transduction Link of Non-alcoholic Steatohepatitis Rats

目的观察红景天苷、姜黄素、绞股蓝总苷、白术多糖(HJJB)复方对非酒精性脂肪性肝炎(NASH)大鼠胰岛素信号转导环节的干预作用。方法采用高脂饮食; 14周诱导的大鼠胰岛素抵抗NASH模型。在造模第9周起,随机分为模型组、西药组(罗格列酮,0.4; mg/kg)和中药组(HJJB)。干预6周后,观察肝组织病理变化(HE染色),检测肝组织TG含量、ALT活性、血清空腹胰岛素(FINS)含量、空; 腹血糖(FBG)含量、胰岛素抵抗指数(HOMA-IR),检测肝组织胰岛素受体底物1 (IRS1 )、磷酸化IRS1 (pIRS1; )、磷脂酰肌醇-3-激酶(PI3K)、磷酸化PI3K(pPI3K)、蛋白激酵B(PKB)、磷酸化PKB(pPKB)蛋白含量;检测肝组织IRS1、; PI3K、PKB mRNA水平。结果与正常组比较,模型组出现肝细胞脂肪变性, TG、ALT、FINS、FBG 及 HOMA-IR 升高(P; <0. 01), IRS1、plRS1、PI3K、pPI3K、PKB、pPKB 蛋白及 IRS1、 PI3K、PKB mRNA降低(P; <0.01)。与模型组比较,中药组和西药组上述病理改变明显减轻,血清TG、ALT、 FINS、FBG 及 HOMA-IR; 含量降低(P<0.05)。中药组 IRS1、pIRS1、PI3K、pPI3K、PKB、pPKB 蛋白及 IRS1、 PI3K、PKB; mRNA水平较模型组及西药组升高(P <0.01,P <0.05),TG及ALT较西药组降低(P <0. 01; )。结论HJJB复方可上调NASH大鼠肝脏IRS1基因表达和蛋白含量,改善PI3K/PKB信号通路。Objective To observe the intervention effect of HJJB; compound(salidroside, curcumin, gypenosides and atractylodes; polysaccharides) on insulin signal transduction link of non-alcoholic; steatohepatitis (NASH) rats. Methods SD male rats were induced by; high-fat diet for 14 weeks for insulin resistance NASH model. From the; ninth week, the rats were divided into the model group, the Western; medicine(WM) group (rosiglitazone, 0. 4 mg/kg) and the Chinese medicine; (CM)group (HJJB) at random .Six weeks after medication, liver pathology; (HE staining), hepatic TG content, serum ALT activity, serum fasting; insulin (FINS), serum fasting blood glucose( FBG), insulin resistance; index (HOMA-IR) were observed. Protein content of hepatic insulin; receptor substrate insulin receptor substrate 1 (IRS1), phosphorylation; of IRS1 (pIRS1),phosphatidylinositol-3 kinase (PI3K) , phosphorylation; of PI3K(pPI3K), protein kinase B (PKB) and phosphorylation of PKB (pPKB); were detected. mRNA expression of hepatic IRS1,PI3K, PKB were also; detected. Results Significant hepatic steatosis were observed in the; model group. TG, ALT, FINS, FBG and HOMA-IR of model group were higher; than those of the normal group(P < 0. 01). Hepatic IRS1,pIRS1 ,; PI3K,pPI3K, PKB, pPKB protein expression level and IRS1 , PI3K,PKB mRNA; level were lower than those of the normal group (P <0. 01). Hepatic; pathological changes in the CM group and WB the group were meliorated,; ALT, FINS, FBG, HOMA-IR and TG of the CM group and the WM group were; lower than those of the model group(P <0. 05). Hepatic; IRS1,pIRS1,PI3K,pPI3K, PKB, pPKB protein expression level and IRS1,; PI3K, PKB mRNA of the CM group were higher than those of the model group; and the WM group(P <0. 01,P <0. 05),ALT and TG of the CM group were; lower than those of the model group (P <0. 01 ). Conclusion HJJB; Compound can significantly increase hepatic IRS1 gene expression and; protein content of fatty liver in rat, and then improve the PI3K/PKB; signal pathways.国家自然科学基金资助项目; 浙江省自然科学基金资助项目; 浙江省中医药科技计划项

Research of prevention and treatment of herb components HJJB compound on non-alcoholic steatohepatitisin rats induced by high-fat diet

目的:探讨中药组分HJJB方(红景天苷、姜黄素、绞股蓝总苷、白术多糖)对高脂饮食诱导的大鼠非酒精性脂肪性肝炎的防治作用。方法:采用高脂饮食14周; 诱导大鼠非酒精性脂肪性肝炎模型。在造模第9周起,随机分为模型组,HJJB方高、低剂量组,罗格列酮组,灌胃给药6周。观察肝组织病理变化(HE染色); ,肝组织甘油三酯(TG)、游离脂肪酸(FFA)含量的变化,血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、谷氨酰转肽酶(GGT)活性及TG、总胆; 固醇(TC)含量的变化。结果:模型组肝组织出现显著的肝细胞脂肪变性及空泡样变,肝组织TG、FFA含量较正常组显著升高(P<0.01),血清ALT; 、AST、GGT活性及TG、TC含量较正常组亦明显升高(P<0.01)。HJJB方高、低剂量组的上述病理改变显著减轻,肝组织TG、FFA含量及血; 清ALT、AST、 GGT、TG、TC水平显著低于模型组(P<0.01),其中HJJB方高剂量组的肝组织TG、FFA含量和血清ALT、AST、; GGT活性显著低于HJJB方低剂量组和罗格列酮组(P<0.05,P<0.01)。结论:中药组分HJJB方对高脂饮食诱导的大鼠非酒精性脂肪性肝炎具; 有良好的防治作用。Objective: To discuss the prevention and treatment of HJJB (salidroside,; curcumin, gypenoside and atractylodes macrocephala polysaccharide); compound on non-alcoholic steatohepatitisin rats induced by high-fat; diet. Methods: Non-alcoholic steatohepatitis model was induced by; high-fat diet for 14 weeks. From the ninth week, the rats were randomly; divided into model group, HJJB high-dose group, HJJB low-dose group and; rosiglitazone group, and were given gavage for six weeks. The observing; items including: pathological changes of liver tissue (HE staining); the; changesof contents of liver tissue triglyceride (TG) and free fatty acid; (FFA); the activities of serum alanine aminotransferase (ALT), aspartate; aminotransferase (AST), glutamyl transpeptidase (GGT) and contents of; serum total cholesterol (TC) and TG. Results: Significant hepatocellular; steatosis and vacuolar degeneration were observed inthe liver tissue of; the model group. The contents of TG and FFA in liver tissue of model; group were significantly higher than those of normal group (P<0.01), and; the activities of serum ALT, AST, GGT and the contents of TG and TC of; model group were higher than those of normal group too (P<0.01). Hepatic; pathological changes in the HJJB compound high-dose, low-dose groups; were all significantly meliorated. The levels of liver TG, FFA and serum; ALT, AST, GGT, TG and TC of HJJB high-dose group, HJJB low-dose group; were significantly lower than that of model group (P<0.01). In addition,; the contents of liver TG and FFA and serum ALT, AST, GGT of HJJB; compound high-dose group were lower than those of HJJB compound low-dose; and rosiglitazone group (P<0.05, P<0.01). Conclusion: HJJB compound does; well in the prevention and treatment of non-alcoholic steatohepatitis; induced by high-fat diet.国家自然科学基金项目; 浙江省自然科学基金项目; 浙江省中医药科技计划项

《土木工程概论》省级精品课程建设的体会及其对教学改革的启示

本文结合"土木工程概论"省级精品课程的建设过程,探讨了该课程在建设中如何体现土木工程专业应用型人才培养的几点经验,及下一步教学改革的努力方向。为该专业其它后续课程的建设以及如何突出应用型人才培养的目标提供了有益的借鉴

The metabolic profilings study of serum and spinal cord from acute spinal cord injury rats ^1H NMR spectroscopy

目的：采用-1H NMR核磁共振代谢组学的方法研究急性脊髓损伤模型大鼠的代谢组学特征及生物标志物,探讨核磁共振代谢组学应用于脊髓损伤研究的可行性。方法：取8周龄清洁级雄性SD大鼠20只,体重（200±10）g,按照随机数字法分为假手术组和模型组,每组10只,模型组采用改良的Allens法制作急性脊髓不完全损伤模型,假手术组不损伤脊髓,术后第1、5、7天采用BBB运动功能评分法进行行为学观察,术后第7天收集脊髓组织作病理学观察,核磁共振代谢组学对两组大鼠血清和脊髓样本进行代谢组学分析。结果：BBB评分显示假手术组术后后肢运动无明显改变,各时间点差异无统计学意义,模型组大鼠术后双下肢呈迟缓性瘫痪,BBB运动评分较低,各时间点差异存在统计学意义,两组运动功能评分在各时间点的差异均有统计学意义;病理切片显示假手术脊髓结构正常,神经分布均匀,模型组脊髓组织结构紊乱,神经元数目减少,存在炎性细胞浸润和空腔坏死组织。代谢组学分析表明,血清中极低密度脂蛋白（VLDL）、低密度脂蛋白（LDL）、谷氨酰胺（glutamine）、柠檬酸（citrate）、二甲基甘氨酸（DMG）等物质和脊髓中谷胱甘肽（glutathione）、3-羟基丁酸（3-OH-butyrate）、N-乙酰天冬氨酸（NAA）、磷酸胆碱（GPC）、谷氨酸（glutamate）、抗坏血酸（ascorbate）等物质浓度有明显变化（P〈0.05）。结论 ：通过对假手术组和模型组大鼠血清和脊髓样本进行代谢组学检测和分析得到了两组样本的差异性代谢物质,有助于解释急性脊髓损伤后血清和脊髓组织中的特异性小分子物质的变化规律,为后期针对性地研究这些代谢标记物在急性脊髓损伤中的作用提供研究基础。Objective： To establish the rat model of acute spinal cord injury,followed by aprimary study on this model with 1H NMR based on metabonomics and to explore the metabonomics and biomarkers of spinal cord injury rat.Methods： Twenty eight-week-old adult male SD rats of clean grade,with body weight of （200±10） g,were divided into sham operation group and model group in accordance with the law of random numbers,and every group had 10 rats. The rats of sham operation group were operated without damaging the spinal cord,and rats of model group were made an animal model of spinal cord incomplete injury according to the modified Allen＇s method. According to BBB score to observate the motor function of rats on the 1th,5th,and 7th days after surgery. Postoperative spinal cord tissue was collected in order to pathologic observation at the 7th day,and the metabolic profilings of serum and spinal cord from spinal cord injury rats were studied by 1H NMR spectroscopy.Results： The hindlimb motion of rats did not obviously change in sham operation group,there was no significant difference at each time point;and rats of model group occurred flaccid paralysis of both lower extremities,there was a significant difference at each time; there was significant differences between two groups at each time. Pathological results showed the spinal cord structure was normal with uniform innervation in shame group,while in model group,the spinal cord structure was mussy,and the neurons were decreased,with inflammatory cells and necrotic tissue. Analysis of metabonomics showed that concentration of very low density fat protein （VLDL）,low density fat protein （LDL）,glutamine,citric acid,dimethylglycine （DMG） in the serum and glutathione,3-OH-butyrate,N-Acetyl-L-aspartic acid （NAA）,glycerophosphocholine （GPC）,glutamic acid,and ascorbate in spinal cord had significant changes（P〈0.05）.Conclusion： There are significant differences in metabolic profile from serum and spinal cord sample between model group and sha浙江省自然基金（编号：LY15H270003）;浙江省中医药科技计划项目（编号：2015ZZ017