温肾固疏方对绝经后骨质疏松大鼠骨代谢以及脂代谢的影响

目的探讨温肾固疏方改善骨质疏松和脂代谢异常的的作用机制。方法将60只大鼠的卵巢全部切除以建立绝经后骨质疏松模型,随机分为对照组(n=20)、雌激素组(n=20)和实验组(n=20)。假去势组(n=20)大鼠仅从卵巢周围切除少量脂肪。干预治疗8周后,采用酶联免疫法测定各组大鼠血清PING、TRACP5b、OPG、BGP的水平;并检测各组大鼠血脂指标。结果与假去势组大鼠比较,对照组大鼠的股骨和股骨近端的BMD明显降低(P0.05);骨代谢指标和脂代谢指标水平均明显恶化(均P0.05)。灌胃治疗后,与对照组比较,雌激素组和实验组大鼠的股骨和股骨近端的骨密度水平明显升高(P0.05),并且两组大鼠的PING、TRACP5b、BGP水平均较显著提高(均P0.05),而OPG水平显著降低(P0.05)。此外,雌激素组和实验组大鼠的脂代谢指标水平均较对照组明显改善(均P0.05)。结论温肾固疏方通过有效提高绝经后骨质疏松大鼠的骨密度,调节骨代谢和脂代谢指标水平,达到改善骨质疏松和调节血脂代谢的效果。     

绝经后2型糖尿病患者血清25(OH)D、Leptin与骨代谢的相关性

目的探讨绝经后2型糖尿病(type 2 diabetes mellitus,T2DM)女性患者血清25-羟维生素D(25-hydroxyvitamin D,25(OH)D)、瘦素(leptin,LEP)水平与骨代谢之间的关系。方法选取遵义医学院附属医院内分泌科住院的绝经后T2DM女性患者130例,根据骨密度分为骨量正常组(A组,n=40)、骨量减少组(B组,n=45)和骨质疏松组(C组,n=45),同期选取50名健康绝经后女性作为空白对照组(NC组,n=50)。收集所有受试者临床资料及生化指标,测定血清25(OH)D、LEP、β-胶原降解产物(β-Crosslaps,β-CTX)、I型胶原N-端前肽(N-aminoterminal propeptide of type I collagen,PINP)及骨钙素(bone gla protein,BGP)水平。Spearmen相关分析绝经后T2DM合并骨质疏松症(osteoporosis,OP)患者血清骨代谢指标的相关因素分析;Logistic回归分析绝经后T2DM患者合并OP的影响因素。结果①与NC组比较,A、B、C三组中25(OH)D、PINP、BGP水平均明显降低,而LEP、β-CTX水平明显升高(P0.05);②与A组比较,B组、C组中25(OH)D、PINP水平均明显降低,而LEP、β-CTX、BGP水平明显升高(P0.05);③与B组比较,C组中25(OH)D、PINP水平均明显降低,而LEP、β-CTX、BGP水平明显升高(P0.05);Spearmen相关分析显示,血清25(OH)D与PINP呈正相关,与β-CTX呈负相关,与BGP无明显相关性;血清LEP与PINP呈负相关,与β-CTX、BGP无关;Logistic回归分析显示BMI、HbA1c、25(OH)D、LEP、PINP与β-CTX均是绝经后T2DM患者合并骨质疏松的独立危险因素。结论血清25(OH)D水平的降低及LEP水平的升高,可能共同参与了绝经后T2DM女性患者OP的发生发展。     

骨松益骨方调控Beclin 1/Bcl-2对去卵巢大鼠骨细胞凋亡和自噬的影响

目的 探讨骨松益骨方(GSYG)对去卵巢(OVX)大鼠骨质疏松的作用以及对Beclin 1/Bcl-2介导的骨细胞凋亡与自噬的影响。方法 将大鼠随机分成假手术组(Sham)、模型组(Model)、GSYG低、中、高剂量组[1.25、2.5、5 g/(kg·d)]。通过ELISA检测大鼠血清中P1NP和β-CTX的水平;Micro-CT测定股骨骨密度以及微结构的变化;HE染色检查骨组织的形态学变化;TUNEL染色观察骨细胞凋亡;免疫组化观察骨组织中LC3的变化;Western blot法检测大鼠胫骨近端Bcl2、Bax、cleaved caspase-3、cleaved PARP、LC3、Beclin1的表达变化;免疫共沉淀法检测Beclin1和Bcl-2的相互作用。结果 与模型组相比,GSYG中、高剂量组的P1NP和β-CTX水平显著降低(P<0.01);GSYG各剂量组骨的微结构明显改善(P<0.01);骨小梁明显增多;骨细胞凋亡明显减少(P<0.01);Bcl-2的表达显著升高(P<0.01),Bax表达显著降低(P<0.05或P<0.01),G...     

不同骨量状态下绝经后初诊2型糖尿病患者血清中MMP-2水平及意义

目的通过检测不同骨量状态下绝经后初诊2型糖尿病(type 2 diabetes mellitus,T2DM)女性患者血清中25羟维生素D[25-hydroxyvitamin D,25(OH)D]、基质金属蛋白酶2(matrix metalloproteinases-2,MMP-2)水平,初步探讨它们在T2DM合并骨质疏松发生发展过程中的作用及意义。方法收集2016年10月至2017年10月我院内分泌科住院的绝经后T2DM患者130例,据骨密度分3组:T2DM骨量正常组(A组45例)、T2DM骨量减少组(B组40例)、T2DM骨质疏松组(C组45例),收集同期我院体检中心年龄、性别相匹配的健康体检者为正常对照组(NC组50例)。采用酶联免疫吸附(ELISA)法测定所有受试者血清MMP-2。Pearson相关分析绝经后T2DM合并骨质疏松(osteoporosis,OP)患者血清MMP-2与各指标的相关性;Logistic回归分析绝经后T2DM患者骨密度的影响因素。结果 (1)A组与B组比较,25(OH)D、PINP、HDL-C水平明显升高,而MMP-2、β-CTX、BGP、Hb A1c、HOMA-IR明显降低,差异有统计学意义(P0.05),FBG、LDL-C、TC、TG、FINS、病程比较,差异无统计学意义(P0.05);(2)C组与NC组比较,MMP-2、FBG、Hb A1c、HOMA-IR、LDL-C、TG、TC、β-CTX水平明显升高,而25(OH)D、HDL-C、PINP、BGP明显降低,差异有统计学意义(P0.05)。结论绝经后T2DM合并骨质疏松患者血清中MMP-2、β-CTX、BGP水平明显升高,而25(OH)D、PINP水平明显减低,提示高水平的MMP-2及低水平的25(OH)D可能共同参与了绝经后T2DM合并OP的发生发展。     

虫草素通过调节COX-2/PGE2信号通路促进骨质疏松大鼠的骨折愈合

目的 探讨虫草素（Cordycepin）调控环氧化酶2（COX-2）/前列腺素E2（PGE2）信号通路对骨质疏松大鼠骨折愈合的影响。方法 制备骨质疏松大鼠模型,将大鼠分为Sham组、Model组、Cordycepin组（10 mg/kg腹腔注射）、Cordycepin+NS-398组（腹腔注射10 mg/kg的Cordycepin+10 mg/kg的COX-2抑制剂）,分别检测骨折愈合情况、骨密度（BMD）及生物力学性能,HE染色观察骨痂组织病理学变化,ELISA法检测血清ALP、CTX-Ⅰ、OC水平及骨痂组织COX-2、PGE2、cAMP水平,免疫组化法检测骨痂组织COX-2、VEGF表达。结果 与Sham组比较,Model组骨折线明显,X光片评分、BMD、骨最大负荷与刚度、ALP、OC水平显著降低、骨组织COX-2、PGE2、cAMP、VEGF表达水平显著降低,CTX-Ⅰ水平显著升高（P＜0.05）;与Model组比较,Cordycepin组X光片评分、BMD、骨最大负荷与刚度、ALP、OC水平显著升高、骨组织COX-2、PGE2、cAMP、VEGF表达水平显著升高,CTX-Ⅰ水平显著降低（P＜0.05）;NS-398可逆转Cordycepin对骨质疏松大鼠骨折愈合的促进作用。结论 虫草素可能通过激活COX-2/PGE2信号通路,促进骨质疏松大鼠的骨折愈合。     

辛伐他汀联合阿仑膦酸钠对去卵巢骨质疏松大鼠骨代谢的影响

目的探讨辛伐他汀联合阿仑膦酸钠干预对去卵巢大鼠骨质疏松骨代谢的影响。方法 60只雌性SD大鼠随机平均分为5组:假手术组、去势组、辛伐他汀组、阿仑膦酸钠组、联合药物组,首先构建去卵巢大鼠骨质疏松性模型。分别检测骨代谢相关生化指标、氧化应激生化指标和骨组织骨密度(bone mineral density,BMD),HE染色观察骨组织形态学。结果去势组大鼠血清Ca、P、SOD、CAT和骨组织BMD均较假手术组显著降低(P0.05),辛伐他汀组、阿仑膦酸钠组、联合药物组上述指标均较去势组升高,以联合用药组升高最显著(P0.05)。去势组大鼠血清ALP、BGP、PICP、TRAP、GLA、ICIP和MDA较假手术组均显著增高(P0.05),辛伐他汀组、阿仑膦酸钠组、联合药物组上述指标较去势组均降低,以联合用药组降低最显著(P0.05)。去势组股骨骨小梁明显稀疏,连接不完整,大量纤维组织,髓腔内大量空泡状脂肪细胞。联合药物组骨小梁数目明显增多,结构较完整,粗细均匀致密,连接成网状。结论辛伐他汀联合阿仑膦酸钠通过调节去卵巢大鼠骨代谢,抗氧化应激,增加骨密度,改善骨组织结构,发挥抗骨质疏松作用。     

温肾固疏方调控去卵巢大鼠氧化应激及骨代谢指标的机制研究

目的观察温肾固疏方对去卵巢骨质疏松模型大鼠氧化应激及骨代谢指标的影响。方法通过切除大鼠双侧卵巢建立绝经后骨质疏松症模型。造模后,将40只模型大鼠随机分为温肾固疏方高、中、低剂量组、雌二醇组、模型组;假手术组仅切除卵巢旁脂肪组织。干预2月后,检测骨组织形态学改变,测定骨密度,采用ELISA法测定血清PINP、BGP、TRACP5b、RANKL、OPG的含量。比色法检测血清中MDA、CAT、SOD水平。结果与假手术组比较,模型组股骨近端和股骨总BMD均明显降低,模型组血清MDA活力明显升高(P0.05),而CAT活力下降明显(P0.01),血清TRACP5b、BGP、PINP含量明显升高(P0.01),而OPG、OPG/sRANKL比值下降(P0.05),骨形态改变与骨质疏松症一致;与模型组相比:各治疗组骨组织形态改善。雌激素组、温肾固疏方高、中剂量组BMD均明显增高(P0.05)。雌激素组、温肾固疏高、中剂量组血清PINP、BGP含量下降(P0.05)。雌激素组、温肾固疏中剂量组TRACP5b含量下降(P0.05)。温肾固疏中、低剂量组血清OPG含量升高(P0.05)。温肾固疏高、中剂量组OPG/sRANKL比值升高(P0.05),低剂量组比值明显升高(P0.01);雌激素组、温肾固疏中剂量组血清MDA活力降低(P0.05),温肾固疏中、高剂量组血清CAT活力升高(P0.05)。结论温肾固疏方可降低骨代谢高转换水平,增加骨形成,减少骨吸收而发挥抗骨质疏松作用,抗氧化应激机制可能在其中发挥了作用。     

雌二醇对去卵巢骨质疏松大鼠骨组织Wnt/β-catenin信号通路的影响

目的观察雌二醇对去卵巢骨质疏松大鼠骨组织Wnt/β-catenin信号通路的影响,探讨其防治绝经后骨质疏松症的作用机制。方法将80只雌性SD大鼠随机分为对照组、假手术组、去势组、药物组,构建绝经后骨质疏松大鼠模型,检测骨组织骨密度(bone mineral density,BMD)和生物力学指标,运用qRT-PCR和免疫组化分别检测骨组织Wnt、β-catenin、BMP-2的mRNA和蛋白表达,通过HE染色观察骨组织形态学。结果去势组股骨BMD、生物力学指标较对照组和假手术组均显著降低(P0.05),药物组股骨BMD、生物力学指标较去势组均显著升高(P0.05)。去势组骨组织Wnt、β-catenin、BMP-2的mRNA和蛋白表达较对照组和假手术组均显著降低(P0.05),药物组骨组织Wnt、β-catenin、BMP-2的mRNA和蛋白表达较去势组均显著升高(P0.05)。去势组骨小梁明显减少,排列稀疏不规则,连接不完整,骨髓腔变大,有大量纤维组织。药物组骨小梁数量减少不明显,粗细均匀稍致密,排列尚规则,连续性完整性较好。结论雌二醇通过Wnt/β-catenin信号通路作用于BMP-2,增加了去卵巢骨质疏松大鼠骨密度,提高了骨生物力学性能,能够改善骨组织结构,发挥了抗骨质疏松作用。     

补肾复方对去卵巢大鼠MEK1、ERK2基因表达的调控 作用

目的研究补肾中药复方(鹿茸、牡蛎、淫羊藿)对去卵巢骨质疏松症大鼠的影响,探讨肾虚骨质疏松症的病理机制,为中医药防治骨质疏松症提供实验依据。方法采用摘除雌性大鼠双侧卵巢的方法复制骨质疏松症模型,以正常组作为标准对照,模型组作为空白对照,盖天力组作为阳性对照,补肾中药复方低、中、高剂量组作为实验组。各用药组灌胃给药12周。采用腹主动脉取血法采集大鼠血清测定血骨钙素(BGP)和抗酒石酸酸性磷酸酶(TRACP),并用DEXA骨密度仪检测左侧股骨骨密度;右侧股骨匀浆提取骨组织中的Total RNA,RT-Real Time PCR,检测MEK1及ERK2的mRNA表达水平。结果模型组BGP水平显著低于正常组(P0.01),TRAP水平较正常组显著升高(P0.01);正常组和补肾中药复方组的股骨骨密度均高于模型组(P0.05);ERK2 mRNA相对表达量明显高于模型组(P0.01),MEK1mRNA相对表达量明显低于模型组(P0.01)。结论补肾中药复方具有防治去卵巢大鼠骨质疏松的作用,其机制与调控MEK1、ERK2基因表达有关。     

rhPTH(1-34)对骨质疏松大鼠的作用及对sclerostin的影响

[目的]探讨人重组甲状旁腺素1-34(rhPTH1-34)对骨质疏松的治疗作用以及与血钙、磷代谢和生长因子的关系。[方法]用摘除大鼠双侧卵巢的方式制备骨质疏松模型,实验动物分为3个组:模型对照组(OVX组,摘除大鼠双侧卵巢不作任何处理);rhPTH1-34治疗组(PTH组,摘除大鼠双侧卵巢12周后用rhPTH1-34治疗8周);假手术组(sham组,仅切除卵巢周围的脂肪组织约3 g,术后12周纳入实验)。应用第4代双能X线骨密度仪测量大鼠股骨上段骨密度值(BMD);用ELISA法测定血清硬化蛋白(sclerostin)水平及骨钙素(BGP)浓度;用自动生化仪测定血清碱性磷酸酶(ALP)。[结果]rhPTH1-34治疗组、sham组均较OVX组股骨上段骨密度增高,组间比较差异有显著性(P<0.01)。rhPTH1-34治疗组血清BGP浓度值升高及sclerostin值降低,与OVX组比较差异有显著性(P<0.01)。各组血清钙、磷含量无明显变化,与OVX组比较差异无显著性,ALP值治疗组与OVX组无明显差异。[结论]rhPTH1-34能够预防股骨上段骨密度丢失,并且血清BGP浓度值升高及sclerostin值降...     

基于BMP-2/SMAD/Runx2通路探究骨化三醇胶囊对大鼠胫骨骨折愈合的影响

目的 探讨骨化三醇胶囊(Cal)通过骨形态发生蛋白2(BMP-2)/SMAD/Runt相关转录因子2(Runx2)通路对大鼠胫骨骨折愈合的影响及相关机制.方法 将52只SD大鼠随机分为对照组(Cont)、胫骨骨折组、Cal组(灌胃10 ng/mL Cal,连续4周)、Cal+Noggin(BMP特异抑制剂)组(灌胃10...     

hi-FGF-2对离体大鼠心缺血/再灌注损伤的拮抗作用

目的 观察高相对分子质量成纤维细胞生长因子-2(hi-FGF-2)对离体大鼠心肌缺血/再灌注损伤的影响.方法 利用Langendorff装置将大鼠心脏给予缺血30 min,再灌注60 min处理.再灌的前10 min经灌流液分别给以生理盐水、hi-FGF-2以及低相对分子质量FGF-2(lo-FGF-2,10μg/10 ml生理盐水).测定左心室收缩压(LVSP)、左心室发展压(LVDP)、左室内压最大变化速率(±dp/dtmax)以及冠脉血流量;采用免疫荧光法检测外源性FGF-2在心肌内的分布和细胞膜上vinculin的变化.结果 与生理盐水组比较,hj-FGF-2和lo-FGF-2两组的心功能包括LVSP、LVDP、±dp/dtmax以及冠脉血流量均显著升高(P＜0.05或0.01);外源性hi-FGF-2或lo-FGF-2在再灌注1 h后广泛分布于心肌.与生理盐水组比较,hj-FGF-2和lo-FGF-2两组的心肌可见密集完整的vinculin荧光染色.结论 hi-FGF-2和lo-FGF-2一样对心肌缺血/再灌注损伤具有拮抗作用.     

P2Y2 receptors and GRK2 are involved in oscillatory fluid flow induced ERK1/2 responses in chondrocytes

Mechanical loading is an important factor regulating cartilage metabolism maintained by chondrocytes. However, some of its underlying mechanisms remain poorly understood. In this study, we employed a chondrogenic cell line ATDC5 to investigate roles of P2Y₂ and GRK2 in chondrocyte mechanotransduction. We first confirmed the expression of chondrocyte markers in differentiated ATDC5 cells. We then exposed both differentiated and undifferentiated ATDC5 cells to oscillatory fluid flow, and found that differentiated ATDC5 cells responded to oscillatory fluid flow by increasing COX‐2 and aggrecan expressions. More importantly, fluid flow induced ERK1/2 response in differentiated cells was increased more than 10 times compared to those in undifferentiated cells. Furthermore, we found that P2Y₂ mRNA and protein levels in differentiated ATDC5 cells were significantly higher than those in undifferentiated cells. In contrast, GRK2 protein levels in differentiated cells were significantly lower than those in undifferentiated cells. Finally, overexpressions of P2Y₂ and GRK2 in differentiated ATDC5 cells result in a 34% increase and a 21% decrease of the ERK1/2 phosphorylation, respectively, in response to oscillatory fluid flow, suggesting important roles of P2Y₂ and GRK2 in chondrocyte mechanotransduction. © 2010 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:828–833     

JAK2-STAT3-波形蛋白信号通路对结肠癌细胞增殖迁移的影响

目的探讨JAK2-STAT3-波形蛋白信号通路在结肠癌细胞增殖迁移中的作用。方法应用JAK2抑制剂AG490处理人结肠癌Lovo细胞株。采用MTT法进行细胞增殖实验：采用细胞划痕实验检测细胞迁移能力;用免疫荧光染色和Western blot检测Lovo细胞中波形蛋白和磷酸化STAT3（P—STAT3）的表达水平。结果AG490处理后,Lovo细胞增殖明显受到抑制．且呈剂量依赖性和时间依赖性（P〈0．05）。细胞划痕后24h,AG490处理组（实验组）的细胞划痕宽度恢复20％,而对照组划痕宽度恢复60％（P〈0．05）。实验组Lovo细胞中P—STAT3和波形蛋白蛋白表达明显降低（P〈0．05）。结论JAK2-STAT3-波形蛋白信号通路参与调控人结肠癌细胞的增殖和迁移。     

Transcutaneous CO2/O2 and CO2/air suction in patients undergoing cataract surgery with retrobulbar anaesthesia

We investigated transcutaneous partial CO2 and O2 pressures and respiratory rate in unpremedicated elderly patients of ASA physical status 1 to 3 who underwent cataract surgery under retrobulbar anaesthesia. In group A no air suction was used. In group B suction was applied under the sterile drapes to avoid rebreathing of CO2. In group A transcutaneous partial CO2 pressure and respiratory rate significantly increased compared with baseline, whereas in group B they remained constant. In both groups transcutaneous partial O2 pressure and oxygen saturation as measured by pulse oximetry significantly rose after insufflating oxygen 31.min-1. Heart rate and mean arterial blood pressure remained constant. Our results demonstrate that the application of suction near the patient's head prevents CO2 rebreathing and subsequent hypercapnia associated with an elevated respiratory rate. The use of suction makes it unnecessary to raise oxygen administration. Suction combined with monitoring of partial CO2 pressure using transcutaneous sensors should be used in all ophthalmological operations under retrobulbar anaesthesia.     

葛根及葛根素对自然衰老小鼠CAT活力及H2O2含量影响的实验研究

目的:研究与探讨葛根对小鼠自然衰老的延缓作用。方法:健康4月龄雌性昆明种小鼠15只,作为青年对照组(A);健康18月龄雌性昆明种小鼠90只,随机分为6组:老年空白对照组(B)、老年阳性对照组(C)、老年葛根中剂量组(D)、老年葛根高剂量组(E)、老年葛根素中剂量组(F)、老年葛根素高剂量组(G)。以灌胃方式给药,以生化分析方法测定过氧化氢酶(CAT)及过氧化氢(H2O2)含量的影响。结果:与青年对照组比较,其余六个老年组CAT的活力下降,H2O2含量显著增高;与老年空白对照组比较,其余五个老年用药组均可提高CAT活性,降低H2O2含量。结论:葛根及葛根素具有延缓小鼠自然衰老的作用。     

HPC2/ELAC2 polymorphism associated with Japanese sporadic prostate cancer

BACKGROUND: HPC2/ELAC2 gene was identified by linkage analysis from familial prostate cancer (Pca) patients in USA. To determine the association of HPC2/ELAC2 gene with Japanese sporadic Pca, we performed a case-control study focused on two missense polymorphisms. METHODS: We genotyped the two polymorphic sites of Ser217Leu and Ala541Thr in sporadic Japanese Pca patients (n = 285) and matched controls (n = 233). Controls were unrelated Japanese outpatients who had no history of any cancer and normal PSA level (less than 4.0 ng/ml). Statistical analyses were performed by Mann-Whitney's U-test, Fisher's exact test, and logistic regression analysis. RESULTS: We observed a significantly higher frequency of the Thr allele at 541 polymorphic site in Pca patients (8.4%) compared to the control group (2.1%) (P = 0.0030, Odds Ratio (OR) = 4.02, 95% CI = 1.50-10.8). However, this SNP does not correlate with clinical stage, PSA level, Gleason score of biopsies or age at diagnosis. No association was identified at Ser217Leu polymorphic site. CONCLUSIONS: Our results indicate that Thr allele at 541 in HPC2/ELAC2 has strong significance in the predisposition of sporadic Pca in Japan. This polymorphism can be useful to predict the personal Pca risk, which lead the effective screening of Pca.     

介入治疗对兔VX2肝癌MMP-2/PCNA/VEGF表达的影响及其意义

目的：模拟不同方法介入治疗对兔VX2肝癌基质金属蛋白酶（MMP-2）、增殖细胞核抗原（PC-NA）、血管内皮生长因子（VEGF）表达的影响。方法：将VX2瘤细胞接种于40只新西兰大白兔肝左叶，建立VX2肝癌模型，随机分为4组，每组10只。介入治疗前MRI测量并记录肿瘤直径。经股动脉途径行肝固有动脉插管，分别注入生理盐水（对照组）、水化碘油（A组）、Ad-p53（B组）、Ad-p53＋水化碘油（C组）。术后1周处死动物，取肿瘤组织制作石蜡切片（HE）染色，镜下观察肿瘤组织坏死情况。免疫组化方法测定MMP-2／PCNA/VEGF的表达。结果：经肝动脉插管介入治疗1周后，A、B、C组肿瘤生长受到明显抑制，与对照组比较，P均〈0.05。单纯碘油栓塞后，肿瘤区的MMP-2、PCNA及VEGF的表达略有升高，与对照组相比P〉0.05；B组与C组的MMP-2、PCNA及VEGF的表达阳性率降低，与对照组相比，P均〈0.05；有转移的MMP-2、PCNA及VEGF的表达阳性率均高于无转移者（P〈0.05）；MMP-2与VEGF、PCNA之间之间有相关性（P〈0.05）。结论：碘油＋Ad-p53可抑制肿瘤的生长，抑制肿瘤新生血管形成，减少转移。MMP-2、PCNA、VEGF的增高预示着肿瘤的高转移、高增殖能力，肿瘤血管的高形成能力。     

Effects of repeated doses of benzodiazepines on arterial blood gases and transcutaneous Po2

The effects of repeated doses of benzodiazepines, diazepam and midazolam in combination with meperidine on arterial blood gases and transcutaneous PO2 were studied in eight healthy volunteers. The study was designed to mimic a clinical situation. Initially two doses of either midazolam 0.05 mg/kg or diazepam in fat emulsion 0.15 mg/kg were given in a randomized crossover fashion with a 20-min interval, followed by meperidine 0.5 mg/kg another 20 min later. The opioid effects were then antagonized by naloxone 0.4 mg. The initial doses of benzodiazepines caused an increase in PaCO2 and a decrease in PaO2. The changes in PaO2 were of short duration and recovered to baseline levels between injections. However, they came sooner and were more pronounced after midazolam. The changes in PtcO2 paralleled those in PaO2. The PtcO2 index as a measure of cardiac output and peripheral blood flow adequacy was increased immediately after the first injection of midazolam but was otherwise not different from control. There were no differences between the drugs concerning PtcO2 index. PaCO2 increased after the first benzodiazepine injection and remained so throughout the study. Addition of meperidine caused only small changes in PaO2 and PaCO2. These changes were reversed by naloxone. In spite of different elimination kinetics there was no difference in the duration of respiratory depression between the two benzodiazepines.