从胰岛微循环探索“脾气散精”环节对血糖稳态的调节机制

减少血糖波动是目前干预糖尿病和预防并发症的重点,也是中医药在糖尿病治疗中的优势所在。越来越多的研究表明,胰岛微循环障碍是胰岛功能下降进而引发血糖波动的关键病理环节,而胰岛微循环局部肾素-血管紧张素系统(renin-angiotensin system,RAS)的过度激活作为胰岛功能失代偿的使动环节,与胰岛内分泌细胞功能密切相关,是研究胰岛功能的关键靶点。中医学认为糖尿病血糖波动与"脾气散精"障碍密切相关,脾不散"精"(血糖),精滞为浊,浊邪壅塞,是血糖稳态失衡的使动环节,亦为糖尿病全病程的关键病机。通过补益"脾"气以促进"胰"中精微物质的布散能够恢复糖调节激素间的平衡,从而减少血糖波动。目前,"脾气散精"对血糖波动的调节机制尚不明确。作者基于以往的临床和科研工作基础,提出"脾气散精"环节通过促进机体胰岛微循环从而发挥其改善胰岛功能、调节血糖稳态的作用,其机制可能与抑制胰岛微循环局部RAS的激活状态相关。RAS系统在胰岛微循环中各信号通路的相互拮抗关系,与中医理论中脾气散精与固精作用的对立制约关系相类似。因此"脾气散精"环节对血糖波动的调节机制有必要从胰岛微循环RAS整体调控的角度进行深入探索,以此揭示中医药调节机体内环境稳态,减少糖尿病患者血糖波动的科学内涵。     

益气化瘀盆炎汤加减治疗盆腔炎气虚血瘀证疗效及对患者血液微循环的影响

目的:探讨益气化瘀盆炎汤加减治疗盆腔炎气虚血瘀证临床疗效及对患者血液微循环的影响。方法:将96例盆腔炎气虚血瘀证患者,随机分为对照组与观察组,各48例。对照组给予左氧氟沙星联合桂枝茯苓胶囊治疗,观察组在对照组治疗基础上给予益气化瘀盆炎汤加减治疗,连续用药2个疗程。比较两组患者临床疗效、治疗前后的中医症候积分、炎性包块直径、盆腔积液深度、血液微循环指标、炎症因子水平、补体C₃和C₄水平,及用药期间的不良反应发生情况。结果:观察组临床治愈率较对照组更高,组间比较差异均有统计学意义(P<0.05)。观察组治疗后的中医症候积分、炎性包块直径、盆腔积液深度均较对照组下降更显著,观察组治疗后的血清ICAM-1、D-二聚体、血浆黏度、红细胞沉降率、血小板聚集率水平均较对照组下降显著,IL-2、IL-10、MMP-2水平均较对照组明显提高,组间比较差异均有统计学意义(P<0.05)。观察组治疗后的补体C₃和C₄水平均较对照组高,组间比较差异具有统计学意义(P<0.05)。两组用药过程中均未见肝肾功能损伤等严重不良反应发生。结论:益气化瘀盆炎汤加减治疗盆腔炎气虚血瘀证疗效较好,其机制可能与改善患者血液微循环、免疫功能及控制炎症因子水平有关。     

Novel cardiovascular magnetic resonance oxygenation approaches in understanding pathophysiology of cardiac diseases

Cardiovascular magnetic resonance imaging (CMR) permits accurate phenotyping of many cardiac diseases. CMR’s inherent advantages are its non‐invasive nature, lack of ionizing radiation and high accuracy and reproducibility. Furthermore, it is able to assess many aspects of cardiac anatomy, structure and function. Specifically, it can characterize myocardial tissue, myocardial function, myocardial mass, myocardial blood flow/perfusion, irreversible and reversible injury, all with a high degree of accuracy and reproducibility. Hence, CMR is a powerful tool in clinical and pre‐clinical research. In recent years there have been novel advances in CMR myocardial tissue characterization. Oxygenation‐sensitive CMR (OS‐CMR) is a novel non‐invasive, contrast independent technique that permits direct quantification of myocardial tissue oxygenation, both at rest and during stress. In this review, we will address the principles of the OS‐CMR technique, its recent advances and summarize the studies in the effects of oxygenation on cardiac diseases.     

桃红四物汤对慢性盆腔炎患者炎性应激及局部微循环状态的影响

目的:观察桃红四物汤对慢性盆腔炎患者炎性应激及局部微循环状态的影响。方法:将2014年5月—2015年2月本院收治的56例慢性盆腔炎患者随机分为对照组和观察组,每组各28例。对照组给予常规西医治疗,观察组给予桃红四物汤治疗。检测两组患者治疗前后细胞因子和血清炎性应激指标水平变化情况。结果:对照组治疗后2周及治疗后4周细胞因子指标和血清炎性应激指标改善情况均优于治疗前,观察组治疗后各期细胞因子和血清炎性应激指标改善情况均优于治疗前,差异均有统计学意义(P0.05);观察组治疗后各指标均优于对照组,差异具有统计学意义(P0.05)。治疗后观察组局部微循环指标优于对照组,差异具有统计学意义(P0.05)。结论:桃红四物汤可显著改善慢性盆腔炎患者炎性应激水平及局部微循环状态。     

模拟失重对成年小鼠闪光视网膜电图和视网膜微循环的影响

目的:小鼠通过悬尾来模拟失重状态下体液头向重分布,然后观察视网膜电图(ERG)和视网膜微循环的变化。方法:正常成年雄性C57BL/6J小鼠随机分到3个实验组和3个对照组,最终每组6只。具体分组如下:实验1组(尾悬15d),实验2组(尾悬30d),实验3组(悬吊30d后恢复体位30d);对照1组(正常饲养15d),对照2组(正常饲养30d),对照3组(正常饲养60d)。时间满足后马上检测暗适应闪光ERG,记录混合反应和振荡电位(OPs),并进行荧光素眼底血管造影(FFA)。然后提取视网膜组织,用免疫组化法检测感光细胞视色素或视蛋白的表达,用TUNEL试剂盒检测视网膜组织细胞的凋亡情况。结果:悬吊15d组,暗适应ERG的混合反应,b波较大而OPs振幅明显降低,后者第二个子波(O 2)幅值197±33μV,15d未悬吊组336±47μV(t=-5.938,P<0.001)。悬吊30d组,小鼠ERG恢复,O 2幅值264±39μV,与30d未悬吊组308±41μV无差异(t=-1.887,P>0.05)。悬吊15d组FFA,视网膜微血管较对照组更密集,呈迂曲扩张的表现,其他实验组基本正常。各实验组感光细胞视色素或视蛋白的表达未见明显异常,视网膜未见凋亡阳性细胞。结论:模拟失重状态下体液头向重分布,短期内小鼠ERG和视网膜微循环可能受到影响,但未对视网膜产生明显的永久性损伤。     

基于“久病入络”理论探讨糖尿病视网膜病变与瘀血的关系

糖尿病视网膜病变(diabetic retinoathy,DR)属于糖尿病微血管并发症之一,近年来,其发病率有逐年升高的趋势。中医根据症状将该病称之为"视瞻昏渺""云雾移睛""暴盲""血灌瞳神",现代医学也称之为"消渴目病"。"久病入络"理论属于络病学说的核心观点之一,其由络病理论发展而来,是清代名医叶天士提出的重要观点。DR是在糖尿病的基础上发展而来,符合"久病入络"之前提,久病必虚且虚久常瘀;同时,络脉逐层分级,延伸到眼部而为目络,目之络脉众多、纤细幽深,络中血行缓慢,易于瘀滞;消渴病暗耗气血津液,目络空虚,气亏血少推动无力,终至瘀血产生。此外,从现代发病机制而言,DR主要与微循环障碍、炎症反应、氧化应激、血液流变学异常、血小板状态等有关,以上机制或可直接产生瘀血,或为瘀血的产生创造了条件。中医学将DR归属于络病范畴,络虚血瘀是其基本病机,瘀血贯穿DR的始终,是DR发生、发展变化的关键因素。"络以通为用"也是叶氏提出的观点之一,已经在诸多学科进行了应用,疗效确切。在治疗本病时,也要严格把握"络以通为用"的基本原则,针对DR之络虚和瘀血,采用补虚通络的方法,配合虫类药、风性药、散结药和入肝经的药,使亏虚之目络得补、瘀滞之目络得通,以达到了改善症状、提高视力、延缓病情进展的目的。     

不同运动量对小鼠微循环及耐缺氧能力的影响

目的：研究不同运动量对小鼠微循环及耐缺氧能力的影响。方法：昆明种小鼠采用转笼法运动4周后，采用BI-2000图像分析系统测定小鼠耳廓微血管管径及血流速度, 采用小鼠急性脑缺血性缺氧实验、亚硝酸钠模型常压耐缺氧实验，观察并记录小鼠断头后张口呼吸时间及耐缺氧存活时间。结果：与空白对照组比较，高运动组小鼠耳廓微动脉、微静脉流速、微动脉管径均显著增加（P<0.05）；中运动组小鼠耳廓微动脉管径均显著增加（P<0.01）；低运动组小鼠耳廓微动流脉速径及微动脉管均显著增加（P<0.05）。高、中、低运动组小鼠断头后张口呼吸时间均显著延长（P<0.05）；高、低运动组和尼莫地平组小鼠亚硝酸钠模型常压耐缺氧时间均显著缩短（P<0.05）。结论：运动训练具有改善小鼠微循环，增强小鼠耐缺氧能力的作用且与运动量有一定的相关性。     

Amelioration of hyperglycemic and hyperosmotic induced vascular dysfunction by in vivo inhibition of protein kinase C and p38 MAP kinase pathway in the rat mesenteric microcirculation

BACKGROUND: Recently, we demonstrated in vivo effects of acutely induced hyperglycemia, diabetes and mannitol infusions on rat mesenteric microcirculation concerning leukocyte-endothelial-cell interaction (Sch?ffler et al. EJCI 28: 886-893, 1998). DESIGN: In this study we have investigated the possible involvement of the protein kinase C (PKC) and p38 MAP kinase cascade as signal transducing elements during hyperglycemic and osmotic stress in an in vivo rat model. RESULTS: Acutely induced hyperglycemia resulted in a significant increase in leukocyte adhesion. This effect could be mimicked by mannitol. Both PKC and p38 MAP kinase were involved in the effects mediated by glucose and mannitol. Acutely induced hyperglycemia resulted in a significant increase in leukocyte emigration. This effect could be imitated by mannitol. However, PKC and p38 MAP kinase were only involved under osmotic stimulation. The hyperglycemia-induced reduction in leukocyte rolling velocity seemed to be a glucose-specific effect, since mannitol did not influence leukocyte rolling velocity. This glucose effect on leukocyte rolling velocity was mediated by an activation of the PKC/p38 MAP kinase cascade. Both hyperglycemia and osmotic stimuli alone were able to reduce venular shear rate without recruitment of the p38 MAP kinase cascade. The observed reduction of shear rate seems to be mediated only by the osmotic effects of glucose via activation of the PKC system. CONCLUSION: The observed effects of glucose on adhesion, emigration and shear rate are due to osmotic effects. The PKC/MAP kinase cascade is involved as a signal transducing component. The reduction of leukocyte rolling velocity is a glucose-specific effect, mediated by the activation of both the PKC and the p38 MAP kinase cascade. Venular shear rate and leukocyte emigration can be influenced by glucose and mannitol due to different regulation mechanisms. It is concluded, that isoform-specific inhibitors of PKC and specific MAP kinase inhibitors represent a potential drug target for preventing microvascular dysfunction in diabetes.     

磺达肝癸钠对高脂血症急性坏死性胰腺炎大鼠微循环及炎症因子影响

目的探讨磺达肝癸钠对高脂血症急性坏死性胰腺炎大鼠微循环及炎症因子影响。方法以健康SD雄性大鼠30只为研究对象,抽签法随机分为治疗组(n=15)和高脂血症组(n=15),两组均通过喂养高脂饲料建立高脂血症大鼠模型,此外治疗组通过将0.1 m L/100 g体重的5%的牛黄胆酸钠溶液注入胰胆管内制成急性坏死性胰腺炎模型,并在建模后0 h、6 h、12 h、18 h注射0.2 m L/100 g次璜达肝癸钠。两组建模后均禁食、禁饮并行2 m L/100 g生理盐水补液。治疗组分别于治疗前和治疗24 h取静脉血用于血清IFN-γ、TNF-α,IL-6和IL-10等炎症因子水平检测,并在治疗前、治疗6 h、12 h和24 h检查比较两组胰体头部和尾部微区血流量。两组建模24 h后均处死剖腹,观察腹腔内组织和胰腺情况,并切除十二指肠内侧胰腺组织行病理检查。结果与高脂血症组比较,治疗组治疗前血清IFN-γ、TNF-α,IL-6和IL-10等炎症因子水平均升高(P0.05)。与治疗前比较,治疗组治疗24 h血清炎症因子水平均降低(P0.05)。与高脂血症组比较,治疗组治疗6 h、12 h和24 h胰体头部和尾部微区血流量均升高(P0.05)。与治疗前比较,治疗组治疗前、治疗6 h、12 h和24 h胰体头部和尾部微区血流量则升高(P0.05)。治疗组水肿、坏死、炎性细胞浸润等胰腺组织病理学评分均高于高脂血症组(P0.05)。结论磺达肝癸钠可改善大鼠微循环及炎症状态。