小剂量链脲佐菌素致大鼠Beta细胞损伤模型探讨

目的 建立小剂量链脲佐菌素（streptozotocin,STZ）致大鼠Beta细胞损伤模型,探讨Beta细胞损伤后胰岛的自身免疫性情况和Beta细胞自我修复能力.方法 SD大鼠腹腔注射40 mg/kg STZ,3d后测量随机血糖、空腹血糖和空腹C-肽,并进行胰腺组织HE染色、胰岛素和CD8α免疫组化染色.于第54天进行口服葡萄糖耐量实验,第56天检测随机血糖、空腹血糖、空腹C-肽和CD8α免疫组化染色.结果 给予40mg/kg剂量STZ处理后,第3天大鼠随机血糖[实验组（33.00± 2.31） mmol/L,空白对照组（5.72±0.63）mmol/L]明显增高,而空腹血糖[实验组（4.03±0.48） mmol/L,空白对照组（3.50±0.41） mmol/L]未见异常,C-肽水平[实验组（0.23±0.03） ng/ml,空白对照组（0.29±0.03） ng/ml]降低,胰岛素免疫组化显示Beta细胞受损,CD8 α免疫组化显示在胰岛的周边部存在阳性细胞表达.56 d时血糖趋势及CD8 α表达与3d时相同,但C-肽水平STZ组高于空白对照组,葡萄糖耐量受损.结论 小剂量STZ损伤大鼠Beta细胞后,Beta细胞分泌功能降低,CD8α阳性细胞持续聚集继续损伤Beta细胞,最终可建立一种轻度损伤的1型糖尿病大鼠模型.     

单次大剂量链脲佐菌素诱导的糖尿病模型β细胞凋亡的研究及意义探讨

目的详细阐述单次大剂量链脲佐菌素（streptozotocin,STZ）诱导的SD大鼠1型糖尿病模型中β细胞凋亡的时相变化。方法 SD大鼠腹腔一次性注射大剂量STZ（65 mg/kg）,观察血糖及胰岛素水平的动态变化,在指定时间点处死大鼠,对胰腺行HE染色、免疫荧光染色及TUNEL染色。结果注射STZ后,SD大鼠血糖呈现出一个高-低-高的三相反应,伴随着胰岛素水平低-高-低的变化以及相应的病理学改变。STZ注射后6 h,β细胞凋亡率（由TUNEL染色衡量）大幅度上升,β细胞凋亡较为同步,此后β细胞凋亡率急剧下降,直到STZ注射后48 h,几乎检测不到β细胞的凋亡。结论单次大剂量STZ诱导的SD大鼠1型糖尿病模型β细胞凋亡在病程早期（STZ注射后6 h）即达高峰,且较为同步,相应出现了血糖水平、胰岛素水平以及胰岛病理结构的变化。     

红景天苷对胰岛β细胞保护作用研究及机制探讨

目的?考察红景天苷的降糖功效及其对胰岛β细胞的保护作用。方法?采用C57BL/6小鼠一次性注射链脲佐菌素（STZ）150mg/kg建立小鼠糖尿病模型,红景天苷剂量为100mg/kg,每日1次灌胃给药,每5日检测小鼠空腹血糖, 30d后检测小鼠胰岛素水平并进行口服糖耐量实验（OGTT）。同时分离正常小鼠胰岛培养3d后,通过Ki67免疫荧光染色及TUNEL染色方法考察红景天苷（50μmol/L）对胰岛β细胞增殖与凋亡的作用。通过RT-PCR方法检测β细胞增殖相关基因insulin、Pdx-1、GLP-1R、IL-1β转录水平变化。结果?与STZ组相比较,红景天苷组（STZ/Sal）能够有效降低小鼠空腹血糖,并表现出胰岛素水平增加的趋势,其OGTT实验也得到显著改善。而小鼠胰岛染色实验表明,红景天苷可以明显促进β细胞增殖,减少高糖诱导的β细胞凋亡。并且红景天苷促进insulin、Pdx-1、GLP-1R 等基因的mRNA水平升高,降低炎症因子IL-1β的mRNA水平。结论?本研究证实红景天苷有效保护胰岛β细胞,促进β细胞增殖并抑制其凋亡,从而实现降低血糖的作用。      

链脲佐菌素诱导急性非糖尿病小鼠胰岛β细胞凋亡模型的建立

目的：以非致糖尿病的小剂量链脲佐菌素（STZ）诱导 BABL/ C 小鼠胰岛β细胞发生凋亡,建立小鼠急性损伤胰岛细胞凋亡的模型,明确其诱导胰岛β细胞凋亡的发生规律,为胰岛β细胞凋亡相关研究提供在体模型。方法选取 BABL/ C 小鼠,分别予生理盐水（对照组）及60、80、100 mg/ kg 小剂量 STZ 一次性腹腔注射（实验组）,观察时点分别为干预后6、12和24 h,动态观察指标为血糖、胰腺 HE 染色观察病理改变以及末端脱氧核苷酸转移酶介导的 dUTP 缺口标记技术（ TUNEL）检测胰岛β细胞凋亡。结果在所有测试时点血糖均在6～11 mmol/ L 范围内波动,未达到糖尿病模型范畴,TUNEL 凋亡检测发现：与对照组相比,实验组各时点的胰岛β细胞凋亡率均明显升高（P ＜0.05）;各实验组均在12 h 时点凋亡率达到最高峰,并且80 mg/ kg 组与60 mg/ kg、100 mg/kg 组相比明显升高（P ＜0.05）。结论非致糖尿病的小剂量 STZ 可成功构建急性非糖尿病小鼠胰岛β细胞凋亡模型,凋亡高峰期在注射后12 h 时点。     

大明胶囊对STZ诱导的1型糖尿病大鼠胰腺microRNA表达谱的影响及其靶点分析

目的 研究大明胶囊(Daming capsule,DM)对链脲佐菌素(streptozocin,STZ)诱导的1型糖尿病大鼠胰腺microRNA (miRNA)表达谱的影响,预测miRNA的靶点并进行分析.方法 将45只成年雄性Sprague-Dawley大鼠随机分为3组:空白组、模型组及DM组.DM组大鼠灌胃给予200 mg/(kg·d)的DM,空白组和模型组给予同等体积的生理盐水,每天2次.2周后,模型组及DM组腹腔注射STZ 65mg/kg建立1型糖尿病模型,注射STZ后DM组大鼠按上述剂量继续给予DM,空白组和模型组给予同等体积的生理盐水,每天2次.STZ注射后3天、7天检测大鼠空腹血糖,并于STZ注射后7天取大鼠胰腺组织.microRNA芯片技术检测各组大鼠胰腺组织miRNA表达,实时荧光定量PCR(real-time PCR,RT-PCR)验证miRNA芯片结果.Targetscan数据库预测miRNA靶点.结果 大鼠腹腔注射STZ 3天和7天后,大鼠空腹血糖值由(6.1±0.6)上升至(21.9±3.1)和(24.6 ±2.4) mmol/L(P ＜0.01).DM组大鼠的空腹血糖为(6.5±0.8) mmol/L,STZ后3天和7天的血糖分别为(14.1±5.1)和(12.4±4.8)mmol/L(P ＜0.01),明显低于同期模型组血糖水平(P＜0.01).在STZ大鼠胰腺,有47个miRNAs表达上调大于2倍,32个miRNAs表达下调大于2倍;DM大鼠胰腺组织,有35个miRNAs表达上调大于2倍,34个miRNAs表达下调大于2倍.其中在STZ大鼠胰腺组织表达上调的21个miRNAs及下调的8个miRNAs的表达被DM逆转;随机选择miR-200b、let-7b和miR-375进行RT-PCR验证的结果显示,这些miRNAs的表达与芯片结果一致;对DM纠正的miRNAs靶点分析发现这些靶点参与了胰腺β细胞胰岛素的生成、分泌和葡萄糖代谢及胰岛细胞凋亡.结论 DM降低了STZ诱导的1型糖尿病大鼠的空腹血糖,并改变了大鼠胰腺组织miRNA表达谱;miRNAs通过调节胰岛素生成、分泌、葡萄糖代谢和胰岛细胞的凋亡参与了DM的降血糖作用.     

链脲佐菌素诱导巴马小型猪1型糖尿病模型对胰岛β细胞凋亡的影响

目的：探讨腹腔多次注射链脲佐菌素（ STZ）诱导的巴马小型猪1型糖尿病模型中β细胞凋亡的变化。方法选用健康雄性巴马小型猪12只,随机分为对照组6只和模型组6只。模型组腹腔注射STZ,第1次腹腔注射STZ 75 mg／kg,1周后第2次腹腔注射STZ 150 mg／kg,对照组注射等量柠檬酸钠溶液;实验结束后观察两组小型猪血糖、胰岛素水平的变化,并进行胰腺组织病理学检查及胰岛β细胞凋亡TUNEL检测。结果（1）造模成功1周后,模型组葡萄糖耐量试验各时点血糖水平均高于对照组的（10.17±1.23）％（P＜0.01）,胰岛素释放实验各时点胰岛素水平均低于对照组（P＜0.01）。（2）模型组胰岛β细胞凋亡率为（33.58±5.67）％明显高于对照组（ P＜0.01）。结论采用腹腔多次注射STZ可以成功构建巴马小型猪1型糖尿病模型,为人类糖尿病研究提供了良好工具。     

穴位埋线抑制2型糖尿病胰岛β细胞凋亡的实验研究

目的：观察穴位埋线对2型糖尿病胰岛β细胞凋亡的影响,探讨穴位埋线治疗2型糖尿病的机制。方法：将造模成功的大鼠按随机化原则分为穴位埋线组、西药组、安慰剂组,同时将普食组大鼠作为正常对照组,每组各10只。穴位埋线组大鼠取双侧胰俞、后三里和中脘等穴,西药组用罗格列酮（0.2mg/kg体重）灌胃,安慰剂组用生理盐水（2mL/kg体重）灌胃,均1次/d,连续4周。观察治疗前后空腹血糖变化,实验结束时,HE染色观察大鼠胰腺组织学改变,免疫组化标记胰岛β细胞,末端脱氧核糖核酸缺口标记法（TUNEL）＋免疫组化法标记凋亡的胰岛β细胞。结果：穴位埋线组、西药组胰岛β细胞凋亡率均明显低于安慰剂组（P=0.000）,穴位埋线组胰岛β细胞凋亡率有低于西药组的趋势,但无显著性差异（P=0.351）。结论：穴位埋线可有效抑制2型糖尿病大鼠胰岛β细胞的凋亡。     

熊脱氧胆酸对糖尿病大鼠胰岛β细胞凋亡的保护作用

目的:探讨熊脱氧胆酸(UDCA)对链脲佐菌素(STZ)诱导的糖尿病(DM)大鼠胰岛β细胞抗氧化及抗凋亡的保护作用.方法:STZ 50 mg/kg一次性腹腔注射建立糖尿病大鼠模型(n=40),并将成功制备的糖尿病大鼠(血糖持续1周≥16.7 mmol/L,n=14)随机分为两组:DM组7只.UDCA组7只.另外取正常对照组10只.自造模成功第10天开始UDCA组以UDCA(40 ms/kg)给大鼠灌胃30天,对照组予等量生理盐水,其间观察各组大鼠的体重、血糖,处死后留取血清和组织标本,测定血清一氧化氮(NO)、丙二醛(MDA),胰腺组织匀浆超氧化物歧化酶(SOD)及观察胰岛β细胞凋亡的形态学改变.结果:糖尿病大鼠在给予UDCA治疗后血糖浓度逐渐下降,但仍然未降到正常水平;糖尿病大鼠予UDCA治疗后减少了由STZ引起的胰岛β细胞的凋亡(P<0.01);血清MDA、NO水平在糖尿病组大鼠显著增加,而胰腺组织匀浆SOD活性则降低;给予UDCA治疗后这些参数均有明显改善.结论:UDCA可以清除STZ产生的NO和氧自由基,保护胰岛β细胞,使其不发生过度凋亡,从而降低血糖.     

GLU-4蛋白表达增加与糖尿病大鼠胰岛素敏感性升高有关

目的：观察葡萄糖转运体-4（GLU-4）蛋白表达对链脲佐菌素（STZ）诱导的2型糖尿病大鼠的血糖、血清胰岛素以及胰岛形态的影响。方法 STZ腹腔注射制备2型糖尿病模型,造模成功28只,存活26只。成模大鼠随机分为4个组：DM对照组（diabetic control group）、低剂量黄连素（Berberine,BBR）治疗组（40 mg/kg）、中剂量BBR治疗组（80 mg/kg）、高剂量BBR治疗组（180 mg/kg）。另选择8只健康大鼠为正常对照组。各组按剂量黄连素每天灌胃8周后,测血糖及胰岛素,计算胰岛素敏感指数（ ISI）、胰岛素抵抗指数（ HOMA-β）指数;HE染色检测胰岛的形态学变化,免疫组化染色检测胰腺组织胰岛中胰岛素（ INS）及GLUT-4蛋白抗原的表达水平。结果⑴DM对照组的空腹血糖（ FBG）、空腹胰岛素（ FINS）显著高于正常对照组（ P ＜0.01）;BBR低、中、高剂量治疗组糖尿病大鼠FBG、FINS均有所下降,高剂量组降FBG、FINS效果更明显（ P ＜0.01）;⑵DM对照组的ISI低于正常对照组（ P ＜0.01）;BBR低、中、高剂量组大鼠的ISI均较DM对照组显著升高（ P ＜0.01）;高剂量组ISI升高更明显（ P ＜0.01）;⑶DM对照组的GLUT-4蛋白抗原低于正常对照组（ P ＜0.05）;低、中、高剂量组GLU-4呈逐步升高趋势,其中高剂量治疗组GLUT-4蛋白抗原较DM对照组显著升高（ P ＜0.01）;⑷DM对照组的INS蛋白抗原低于正常对照组（ P ＜0.05）;低、中、高剂量组INS呈逐步升高趋势,其中高剂量组INS蛋白抗原较DM对照组显著升高（ P＜0.01）。结论经过黄连素治疗后,2型糖尿病大鼠的FBG有所下降,胰岛素分泌有一定的提高,尤为高剂量（180 mg/kg）组明显;2型糖尿病大鼠的胰岛素敏感性亦得到改善;高剂量组2型糖尿病大鼠胰腺胰岛β细胞中胰岛素GLUT-4蛋白增加,提示黄连素可能通过GLUT-4途径促进了组织中葡萄糖的利?     

链脲佐菌素诱发新生期大鼠糖耐量异常与剂量的关系

目的探讨链脲佐菌素（streptozotocin,STZ）诱发新生期大鼠糖耐量动物模型与剂量关系。方法 32只新生期Wistar大鼠生后3d,随机均分为4组,正常对照组腹腔注射0.1mmol/L柠檬酸-柠檬酸钠缓冲液,其余3组分别一次性腹腔注射链脲佐菌素60mg/kg、80mg/kg、100mg/kg,10周后检测空腹血糖及餐后2h血糖,15周后复查。结果 10周时各组与空白组比较,100mg/kg组空腹血糖升高（P〈0.05）;80mg/kg、100mg/kg组餐后血糖升高（P〈0.05）;15周复查时,各组空腹血糖与空白组比较没有统计学差异（P〉0.05）,80mg/kg、100mg/kg组餐后血糖升高（P〈0.05）。结论给予新生期大鼠注射2%STZ溶液80mg/kg,10周符合糖耐量异常的特征,可成功建立糖耐量动物模型。     

APPLICATION OF LORNOXICAM TO PATIENT-CONTROLLED ANALGESIA IN PATIENTS UNDERGOING ABDOMINAL SURGERIES

FOR anesthesiologis s ,treatingpostoperativepainhas alwaysbeen a problem.Althoughopioidshave been provedtobe effective,theirsideeffectscouldnotbeignored.With thedevelopmentofscienceand pharmacology,many drugs with aspectsof satisfactoryanalgesicefficacyand couldbe welltoleratedby patientshave been developed.And lornoxicamisone of them, which isa non-steroidalanti-inflammatorydrug (NSAID ), with analgesic, anti-infl-ammatory,andantipyreticproperties.Itseliminationhalf-time(3 to 5 hours) isle…     

Acupuncture Treatment of Vomiting

CASE HISTORY A female patient, 46 years old, head of the foreign affairs department of a certain university in Beijing, paid her first visit on October 9, 2006, with the chief complaint of vomiting for one month. She got vomiting after meals in early September. Before that, she had discomfortable sensation in the stomach due to angry with others, but she didn't pay much attention. Later, it developed into vomiting after eating. After the vomiting, the discomfort would be relieved, but with slight hypodynamia. She was once diagnosed as having 'neurogenic vomiting'. Having taken some western and Chinese drugs, the above symptoms were a little bit improved, but she would have nausea upon eating and with regurgitation. Because of the fear for vomiting, she did not dare to have food intake, with body weight reduction of 6 kilos in one month.     

Qiu Baoguo''''s Experience in Treating Consumptive Syndromes after Radio-Chemotherapies

Radiotherapy and chemotherapy are the important modern medical therapies for malignant tumors,yet they can also bring about serious local and systemic toxic side reactions so to decrease the patient;'s life quality,manifested by a series of consumptive symptoms.Having engaged in the combined work of Chinese and western medicine for nearly 50 years,the research fellow Qiu Baoguo in Henan Provincial Academy of TCM has developed his unique views on the TCM study of consumptive syndromes.The author of this essay had once the fortune tO follow Dr.Qiu in clinic,and specially would like to introduce in the following Dr.Qiu's experience in treating consumptive syndromes after radio-chemotherapies for patients with malignant tumor.     

Insomnia Due to Deficiency of Both the Heart and Spleen Treated by Acupuncture-Moxibustion and Chinese Tuina

OBJECTIVE: To observe therapeutic effects of the comprehensive therapy of acupuncture-moxibustion and Chinese Tuina for treatment of insomnia due to deficiency of both the heart and spleen. METHODS: 92 cases were divided randomly into the treatment group (treated by acupuncture-moxibustion and Chinese Tuina) and the control group (treated by acupuncture-moxibustion). RESULTS: The therapeutic effect of the treatment group was obviously superior to that of the control group (the CHI2 test showed P < 0.01). CONCLUSIONS: The comprehensive therapy of acupuncture-moxibustion and Chinese Tuina can give marked therapeutic effects for treatment of insomnia due to deficiency of both the heart and spleen.     

Analysis of CK-19,PDX-1,Nestin,Ngn3 in different donor islet purity in rats

Objective: To investigate if there are the CK-19, PDX-1, Nestin, Ngn3 positive cells in the donor islets of different purity in rats. Methods: Thirty male adult SD rats were randomly divided into 3 groups. Islets were isolated using digestion by ductal injection of collagenase. Group Ⅰ (n=10): Separating cell preparations were not purified, Group Ⅱ(n=10): Islet sediment was purified with 25% Ficoll400 ,Group Ⅲ (n=10): Islet sediment was purified with 25% and 11% Ficoll-400. The levels of protein of CK-19, PDX-1, Nestin and Ngn3 were detected by immunohistochemistry and the mRNA of CK-19, PDX-1, Nestin, Ngn3 was amplified by RT-PCR. Results: After two different purification methods applied, three islet preparations of different purities were obtained. The difference of islet purity was significant among various groups (P＜0.05). Compared with group Ⅱ and group Ⅲ,the protein and mRNA of CK-19, PDX-1, Nestin,Ngn3 were both higher in group Ⅰ; group Ⅲ was poorly expressed. Conclusions: The three different islet purity donor islet have different CK-19, PDX-1, Nestin, Ngn3 positive cells within them, indicating that there are some islet stem cells in the purified donor islet.     

Dr.Zhang Ren''''s Experience in the Acupuncture Treatment of Different Diseases with the Same Therapeutic Principle

Dr.Zhang Ren,the chief physician,is the chairman of Shanghai Acupuncture and Moxibustion Association.Having been engaged in medicine for about 40 years,he is experienced in treating various intractable diseases.In his long years of clinical practice,he advocates taking the TCM differentiation as the basis to seek for the acupuncture method for treatment of modern intractable diseases.The author of this essay had the fortune to follow Dr.Zhang in study.The following is a summary of Dr.Zhang's experience in the acupuncture treatment for different intractable diseases with the same therapeutic principle.     

Luo Lingjie''''s Experience in Treating Chronic Nephropathy

In treating chronic nephropathy,Luo Lingjie,a chief physician,pays attention to regulating the balance between yin and yang,treating infection if present,and removing pathogenic factors.He prescribes gentle drugs and uses carefully strongly warming-tonifying ones,emphasizes the importance of persuading the patient to persist in treatment with medication and nurse one's health for recuperation,and is good at combined use of TCM and western medicine therapy and brings the merits of various therapies into full play,with obvious theraoeutic effects.     

Acupuncture Combined with Spinal Tui Na for Treatment of Primary Dysmenorrhea in 30 Cases

Objective: To observe the therapeutic effects in acupunture treatment of primary dysmenorrhea combined with spinal Tui Na, and study its mechanism. Methods: Thirty cases of the treatment group were treated by acupuncture combined with spinal Tui Na, and thirty cases in the control group were treated by routine acupuncture. Results: The total effective rate was 93.3% in the treatment group, and 73.3% in the control group, with a significant difference between the two groups (P<0.05). Conclusions: Acupuncture combined with spinal Tui Na has good prospects for treatment of primary dysmenorrhea.