缺氧预处理对老年大鼠运动性骨骼肌损伤的作用及机制

目的了解缺氧预处理对老年大鼠运动性骨骼肌损伤发生发展的影响。方法将老年雌性SD大鼠随机分为对照组(CON)组、大强度离心跑台运动组(EE)组、缺氧预处理+离心跑台运动组(HCP)组,4月龄大鼠作为成年对照组(ADU)组。HCP组大鼠进行1 w的缺氧预处理。将EE组及HCP组大鼠进行一次性大强度离心跑台运动后处死,测定血清白细胞介素(IL)-6含量、肌酸激酶(CK)、乳酸脱氢酶(LDH)含量,石蜡切片观察肌纤维细微结构;取肌肉匀浆测超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量。结果 EE组及HCP组大鼠运动后均出现骨骼肌损伤现象,EE组损伤较HCP组严重。与EE组相比,HCP组血清IL-6、CK及LDH水平明显降低,比目鱼肌MDA水平明显降低,SOD活性明显升高。结论缺氧预处理可提高老年大鼠骨骼肌的抗氧化能力,降低骨骼肌损伤后炎性反应,对运动性骨骼肌损伤有预防作用。     

下肢缺血预处理调控未成熟心肌细胞凋亡的研究

目的探讨下肢缺血预处理调控未成熟心肌细胞凋亡和对bcl-2、bax、fas表达的影响。方法采用兔离体心脏Langendorff灌注模型,24只幼兔随机分为三组：对照组（c组,n=8）：仅灌注KH液180rain;缺血／再灌组（I／R组,n=8）：心脏灌注20min后,停灌60min,复灌100min;下肢缺血预处理组（LIP组,n=8）,反复3次阻断双下肢血流5min／放开5min,建立Langendorff模型,然后重复I／R组缺血,再灌方法。细胞原位标记与半定量分析细胞凋亡和bcl-2、bax、fas蛋白表达。结果凋亡细胞原位标记与半定量分析：LIP组与I／R组比较,心肌细胞凋亡率明显减少,bcl-2表达明显增多,bax、fas表达明显减少。结论下肢缺血预处理可减少心肌细胞凋亡和调控心肌bcl-2、bax、fas表达。     

培哚普利在糖尿病大鼠肢体缺血后血管再生中的作用

目的探讨培哚普利在1型糖尿病（T1DM）大鼠肢体缺血后血管再生中的作用及相关机制。方法对T1DM大鼠模型予单侧肢体股动脉离断。分为对照（DM）组、培哚普利治疗（DMA）组和培哚普利＋内皮型一氧化氮合酶（eNOS）阻断剂治疗（DML）组。治疗4周后比较各组缺血肢体血管再生情况以及eNOS、血管内皮生长因子（VEGF）、碱性成纤维细胞生长因子（bFGF）的mRNA和蛋白表达水平。结果与正常对照（Nc）组相比,DM组的缺血肢体微血管密度（MVD）、eNOS、VEGF和bFGF的mRNA和蛋白表达均下降,DMA组上述指标明显上调（P均〈0．05）。DML组的MVD、eNOS和bFGF的mRNA和蛋白表达降低（P〈0．05）,而VEGF表达不受影响（P〉0．05）。结论T1DM大鼠的缺血性血管再生受损,与之有关的生长因子表达下调。培哚普利能促进T1DM大鼠缺血肢体的血管再生,其机制与eNOS、VEGF和bFGF的表达上调有关。     

Effects of atorvastatin on autophagy in skeletal muscles of diabetic rats

Aims/Introduction

Atorvastatin is usually used to decrease the amount of fatty substances in individuals with type 2 diabetes mellitus. However, it can cause side‐effects, such as breakdown of skeletal muscle tissue. The present study focused on the effects of atorvastatin on autophagy of the skeletal muscles in diabetic rats.

Materials and Methods

Diabetes in rats in the diabetic (D) and atorvastatin (T) groups was induced using streptozotocin (65 mg/kg, intraperitoneal injection). Next, rats in the T group were treated with atorvastatin (10 mg/kg/day, intragastric administration), whereas rats in the control and D groups were given water. Additionally, the rats in T and D groups were fed a high‐fat and high‐sugar diet for 10 weeks. Subsequently, the histopathological changes, and expression levels of microtubule‐associated protein 1 light chain 3 (LC3)‐I/‐II and p62 in the skeletal muscle specimens in the three groups were analyzed.

Results

Rats in the T group had reduced lipid droplets, cholesterol and low‐density lipoprotein (P < 0.05) levels than those in the D group. Disordered atrophic myocytes, incrassated vascular walls and decreased cross‐sectional area of type I fibers were found using hematoxylin–eosin and adenosine triphosphatase staining in the D and T groups. The messenger ribonucleic acid and protein levels of LC3‐II and the LC3‐II/LC3‐I ratio were increased in the T group compared with those in the other groups (P < 0.05), whereas the protein level of p62 showed the opposite trend.

Conclusions

Atorvastatin enhanced the autophagy level of skeletal muscles to decrease lipid deposition, which possibly exacerbated myopathy.     

Fiber atrophy and hypertrophy in skeletal muscles of late middle-aged Fischer 344 x Brown Norway F1-hybrid rats

We examined young adult and late middle-aged male rats to test the hypothesis that gastrocnemius (a locomotor muscle) demonstrates reduced fiber size with aging, whereas soleus (a postural muscle) demonstrates atrophy of some fibers and compensatory hypertrophy in other fibers. Although body mass was greater in late middle-aged animals, mass was reduced in gastrocnemius but not soleus muscle. In another group of animals, physical activity was reduced by 34% in late middle-aged animals. Whereas mean fiber size was lower in gastrocnemius of late middle-aged animals, it was not different in soleus. Histograms revealed atrophied fibers (/=8000 micro m(2)) in soleus with aging. Atrophied fibers often demonstrated no subsarcolemmal mitochondrial staining, suggesting denervation, whereas hypertrophied fibers often demonstrated cytochrome oxidase deficiency, suggesting mitochondrial dysfunction. These results underscore the divergent influences (e.g., physical inactivity, denervation, mitochondrial dysfunction) affecting fiber size with aging.     

红景天酪醇对老年大鼠心肌缺血缺氧型冠心病的影响

目的探讨红景天酪醇对老年大鼠心肌缺血缺氧型冠心病的作用。方法取30只老年大鼠随机分为正常对照组、模型组与给药组,每组10只,采用高脂饮食联合用药的方法,正常对照组喂养基础饲料,模型组与给药组喂养高脂饲料,连续5 w。腹腔注射4%异丙肾上腺素(Iso)5 ml/kg,在通过装有钠石灰缺氧再给氧的装置制造大鼠心肌缺血缺氧冠心病模型,红景天酪醇灌胃给药1 h后,记录心功能,检测血清乳酸脱氢酶(LDH)和肌酸磷酸激酶(CK)及心肌髓过氧化物酶(MPO)和丙二醛(MDA)含量。结果给药组心电图变化较模型组明显改善,LDH和CK水平明显下降,心肌MPO和MDA含量明显降低(均P<0.05)。结论红景天酪醇对老年大鼠心肌缺血缺氧损伤有保护作用。     

阿托伐他汀对急性缺血心肌细胞的保护作用

目的探讨不同剂量的阿托伐他汀预处理对大鼠急性缺血心肌细胞保护作用及其机制。方法雄性SD大鼠40只,随机分为阿托伐他汀高剂量组(20 mg.kg-1.d-1),中剂量组(10 mg.kg-1.d-1),低剂量组(2 mg.kg-1.d-1),对照组(等量生理盐水),每组10只。伊文蓝和TTC染色法确定缺血和梗死心肌的范围;比色法测定心肌组织内的髓过氧化物酶(MPO)、心肌内NO活性;酶动力法测定肌酸激酶同工酶(CK-MB)的活性。结果与对照组比较,阿托伐他汀高、中剂量组可明显减少心肌梗死面积,明显降低CK-MB和心肌内的MPO水平(P<0.01);显著增加心肌内的NO水平(P<0.05)。阿托伐他汀高、中、低剂量组间无明显差异(P>0.05)。结论高、中剂量的阿托伐他汀对急性缺血心肌细胞具有保护作用,机制可能与NO有关。     

吡格列酮对大鼠急性坏死性胰腺炎的干预治疗作用

目的 观察经过氧化酶体增殖因子活化受体7（PPART）配体吡咯列酮预处理后急性坏死型胰腺炎（SAP）大鼠胰腺组织中核因子-κB（NF-κB）和细胞间粘附分子-1（ICAM-1）表达的变化，探讨PPARγ对大鼠SAP的干预治疗作用。方法54只健康雄性Sprague-Dawley大鼠，均分为假手术组（C组）、SAP组（A组）和吡格列酮预处理组（Ⅰ组）。采用逆行胰胆管内加压注射5％牛磺胆酸钠（0．1ml／100g）建立SAP模型。Ⅰ组大鼠在术前2h腹腔内注射吡格列酮（2mg／100g）。分别于术后3、6、12h3个时段采用腹主动脉放血法将大鼠分批处死（每次每组6只），取血、腹水和胰腺组织。采用免疫组化二步法检测胰腺组织NF-κB和ICAM-1的表达，同时进行血清淀粉酶、腹水、胰腺大体病理、组织学评分和胰腺组织含水量测定。结果吡咯列酮预处理可明显减轻大鼠SAP严重程度，血清淀粉酶水平于6h后降低；腹水量减少；胰腺组织大体和病理评分6h后降低；组织含水量逐渐减少。吡咯列酮预处理后大鼠胰腺组织中ICAM-1表达减弱、NF-κB活性受到抑制（P值均〈0．05）。结论吡咯列酮具有减轻SAP效应，可能是通过抑制NF-κB活性和ICAM-1表达起到抗炎作用，有望成为一种临床治疗SAP的有效新方法。