大黄丹参对高脂饮食诱发的胰腺纤维化大鼠影响的研究

目的:研究大黄丹参对高脂饮食诱导的胰腺纤维化大鼠氧化应激、内质网应激相关因子的影响。方法:将40只雄性清洁级SD大鼠,采用随机数表法均分成对照组、模型组、大黄丹参低、中、高剂量组,每组8只;对照组喂以普通饲料,其余4组均喂以高脂饲料连续10周建立胰腺纤维化模型。造模同时,各组以相应药物灌胃,对照组与模型组生理盐水灌胃,...     

高脂饮食诱导小鼠脂肪肝

目的 初步探索高脂饮食对小鼠肝脏的损伤情况.方法 40只小鼠随机分为2组,实验组给予高脂饮食,对照组正常饮食.1个月后,采用颈椎处死法,将取出的肝脏进行病理学观察以及肝脂的测定.结果 实验组和对照组相比,肝重、肝重/体重、肝脂、肝脏大体标本和肝脏病理组织学观察差异在统计学上均具有显著性意义.结论 高脂饮食可能在小鼠脂肪肝的发生中起到一定的作用,但有必要开展各种不同类饮食的混合喂养以及剂量反应关系的研究.     

高脂高糖饮食暴露诱导大鼠多囊卵巢综合征研究

目的通过高脂高糖饮食诱导雌性大鼠多囊卵巢综合征(PCOS),探讨其生殖和代谢特征。方法将23天断奶雌性大鼠随机分成两组:对照组接受正常饮食(对照组,n=18),实验组接受高脂高糖饮食(HFHS组,n=18),连续喂养14周。观察两组体重、动情周期和卵巢组织学变化,检测两组空腹血糖、空腹胰岛素、计算胰岛素抵抗指数(HOMA-IR)、血脂水平、性激素水平。结果 HFHS组大鼠体重至第3周起显著高于对照组(P0.001),但两组卵巢重量无显著差异[(0.041±0.006)g vs.(0.045±0.005)g,P0.05]。HFHS组动情周期失去规律变化,发情期持续时间占整个发情周期时间的比例显著长大对照组[(0.46±0.06)vs.(0.27±0.03),P0.001]。HFHS组卵巢组织学检查发现多个囊状扩张卵泡、黄体数量下降。HFHS组空腹胰岛素、HOMA-IR、总胆固醇水平显著高于对照组(P0.001);发情间期HFHS组LH和E2水平显著低于对照组(P0.05),睾酮(T)水平显著高于对照组(P0.001);发情前期HFHS组LH和P水平显著低于对照组(P0.05),T和E2水平显著高于对照组(P0.001)。结论高脂高糖饮食诱导雌性大鼠PCOS,并产生代谢紊乱和卵巢改变,与PCOS患者临床观察到的相似。     

长期高脂饮食诱导大鼠胰腺损伤的形态学演变

本研究通过对高脂饮食诱发的大鼠胰腺形态结构变化进行动态观察,为进一步探索长期高脂饮食与胰腺损害的发生机制提供研究基础.     

长期高脂饮食诱导大鼠胰腺损伤的形态学演变

本研究通过对高脂饮食诱发的大鼠胰腺形态结构变化进行动态观察,为进一步探索长期高脂饮食与胰腺损害的发生机制提供研究基础.     

长期高脂饮食诱导大鼠胰腺损伤的形态学演变

本研究通过对高脂饮食诱发的大鼠胰腺形态结构变化进行动态观察,为进一步探索长期高脂饮食与胰腺损害的发生机制提供研究基础.     

长期高脂饮食诱导大鼠胰腺损伤的形态学演变

本研究通过对高脂饮食诱发的大鼠胰腺形态结构变化进行动态观察,为进一步探索长期高脂饮食与胰腺损害的发生机制提供研究基础.     

长期高脂饮食诱导大鼠胰腺损伤的形态学演变

本研究通过对高脂饮食诱发的大鼠胰腺形态结构变化进行动态观察,为进一步探索长期高脂饮食与胰腺损害的发生机制提供研究基础.     

长期高脂饮食诱导大鼠胰腺损伤的形态学演变

本研究通过对高脂饮食诱发的大鼠胰腺形态结构变化进行动态观察,为进一步探索长期高脂饮食与胰腺损害的发生机制提供研究基础.     

长期高脂饮食诱导大鼠胰腺损伤的形态学演变

本研究通过对高脂饮食诱发的大鼠胰腺形态结构变化进行动态观察,为进一步探索长期高脂饮食与胰腺损害的发生机制提供研究基础.     

自主运动对高脂饮食诱导的肥胖小鼠膝骨关节炎软骨形态学的影响

目的研究高脂饮食诱导的骨性关节炎发生过程中骨关节软骨病变以及自主运动对骨性关节炎软骨的影响机制,探讨自主运动对膝骨关节炎软骨的保护作用,为临床治疗膝骨关节炎提供有效的实验证据。方法将28只C57BL/6 J小鼠随机分为正常饮食组(C-Sed组,n=6)、正常饮食加运动组(C-Ex组,n=6)、高脂饮食组(HF-Sed组,n=8)及高脂饮食加运动组(HF-Ex组,n=8)。C-Sed组和C-Ex组喂养基础饲料(13.5%Kcal),HF-Sed组和HF-Ex组喂养高脂饲料(60%Kcal)。喂养8周后,C-Ex组和HF-Ex组小鼠采用自主转轮运动进行干预,记录运动数据,运动3周后行颈椎脱臼处死;C-Sed组和HF-Sed组小鼠不进行运动干预,继续喂养不同膳食4周后行颈椎脱臼处死,取膝关节软骨组织进行固定、脱钙,制成4μm厚石蜡切片,并进行HE及甲苯胺蓝染色,测量各组小鼠软骨层厚度,探究自主转轮运动对肥胖小鼠膝骨关节炎软骨形态学的影响。结果喂养12周结束后,与C-Sed组小鼠相比,HF-Sed组小鼠体重明显增加,高脂饮食成功诱导了高脂饮食组小鼠发生肥胖,且经HE及甲苯胺蓝染色后,可观察到与C-Sed组小鼠相比,HF-Sed组小鼠软骨表面粗糙、部分缺损,软骨层厚度降低(P0.001);而HF-Ex组较HF-Sed组小鼠关节软骨表面光滑,软骨层厚度增加,Mankin评分分值降低。结论 3周自主转轮运动可增加高脂组小鼠软骨层厚度,降低Mankin评分分值,延缓骨关节炎软骨退变,起到保护关节软骨的作用。     

丙泊酚对大鼠小肠缺血-再灌注后肺损伤氧自由基变化的影响

目的 探讨不同临床剂量丙泊酚对大鼠小肠缺血-再灌注后肺损伤氧自由基变化的影响及其保护作用。方法 雄性SD大鼠40只,随机分为假手术对照组(C组)、小肠缺血-再灌注组(R组)及分别给予丙泊酚4mg·kg~(-1)·h~(-1)、8mg·kg~(-1)·h~(-1)、10mg·kg~(-1)·h~(-1)(P4、P8、P10)五组;制作小肠缺血-再灌注模型。实验结束即刻留取血样和肺组织,待测脂质过氧化物和肺组织形态学变化。结果 R、P4组血中脂质过氧化物明显升高,与C、P8、P10组相比均有非常显著差异(P<0.01),P8、P10组与C组相比无统计学差异;肺组织脂质过氧化物各实验组与对照组相比差异非常显著(P<0.01),以R组改变最为明显;各用药组指标均得以改善,与R组相比有显著差异(P<0.01),P4与P8、P10组相比亦差异显著(P<0.01)。假手术组肺组织结构正常,R组可见肺泡压闭实变,腔内有大量渗出,炎性细胞浸润,毛细血管扩张,支气管壁增厚,各用药组肺部改变较R组明显减轻,P8、P10两组除了有少量改变外,肺组织结构基本接近正常。结论 氧自由基在大鼠小肠缺血-再灌注后肺损伤中有重要作用,临床剂量丙泊酚不同程度地抑制脂质过氧化反应,对小肠缺血-再灌注后氧自由基介导的肺损伤产生保护作用。     

高脂饲料对不同月龄小鼠骨质疏松的影响

目的 研究高脂饲料对不同月龄小鼠骨质疏松的影响。方法 将雄性C57BL/6J小鼠随机分为6月龄正常饲料组、6月龄高脂饲料组、12月龄正常饲料组、12月龄高脂饲料组。饲养16周后处死,取小鼠血清检测血脂（TC、TG、HDL-C、LDL-C）、氧化应激和炎症（SOD、MDA、IL-6、TNF-α）以及骨代谢标志物（CTX-1、PINP）等指标的水平;取小鼠股骨经Micro-CT和HE染色分析股骨远端微观结构和骨组织形态。结果 与正常饲料组相比,各月龄高脂饲料组小鼠的体重和体脂率增加（P＜0.05）,血清中TC、TG、LDL-C水平增高（P＜0.05）,且在12月龄高脂饲料组中最高。与正常饲料组相比,Micro-CT显示各月龄高脂饲料组小鼠BV/TV、BS/TV降低（P＜0.05）,骨微结构破坏明显;HE染色显示各月龄高脂饲料组小鼠骨小梁减少。饲料相同时,12月龄组小鼠的骨量和骨小梁数目也明显低于6月龄组,且在12月龄高脂饲料组中骨量丢失最为明显。各月龄高脂饲料组小鼠血清中IL-6、TNF-α、MDA水平均较正常饲料组增高（P＜0.05）;6月龄高脂饲料组的血清CTX-1水平高于正常饲料组（P＜0.05）。结论 高脂饮食和高龄可加重小鼠氧化应激和炎症水平,损害小鼠骨健康,且高脂饮食和高龄同时存在时对鼠骨健康的损害作用更为明显。     

Picroside II decreases the development of fibrosis induced by ischemia/reperfusion injury in rats

In kidney transplantation, renal ischemia and reperfusion injury was one of the leading factors to the development of renal fibrosis, which was the main cause of graft loss. The fibrogenic changes were associated with the long term inflammation elicited by ischemia and reperfusion injury. In the present study, we investigated the role of the Picroside II, the main active constituents of the extract of picrorrhiza scrophulariiflora roots, in attenuating renal fibrosis in a renal ischemia and reperfusion injury model. We induced ischemia and reperfusion injury in kidneys treated with or without Picroside II. We observed that inflammation and tissue fibrosis were increased in ischemia and reperfusion injury group compared to Picroside II group, however, these changes were significantly decreased by the treatment with Picroside II. We concluded that Picroside II can protect the ischemic kidney against renal fibrosis and its mechanism may be through the inhibition of the long term inflammation.     

AMPK attenuates inflammation to reduce fibrosis induced by acute ischemia reperfusion injury in mice

Objective To observe the effect of adenosine monophosphate activated protein kinase (AMPK) on attenuating inflammation in fibrosis induced by acute ischemia reperfusion injury (IRI) in mice. Methods Forty eight male C57BL/6 mice were randomly divided into four groups: sham operation group (sham group), IRI group, AMPK inhibitor+IRI group (AMPK/IRI group) and normal saline+IRI group (NS/IRI group), 12 mice each group. The mice with renal IRI were occluded for 30 min through clipping bilateral renal pedicle, then released renal perfusion. Mice in sham group were performed the separation of renal pedicle without clipping. Mice in AMPK/IRI group and NS/IRI group were respectively intraperitoneal injected AMPK inhibitor and normal saline before IRI. At the 2 d after operation, 6 randomly-selected mice from each group were blooded by extraction eyeball to detect BUN and Scr. The renal histopathological changes were observed through HE staining. The mRNA expression of IL-1β, IL-6 and TNF-α was detected by real time PCR, and the level of AMPK phosphorylation was detected by Western blotting. At the 14 d after operation, Collagen 1 (COL1), α-SMA and fibronectin (FN) were detected by immunofluorescence and Western blotting in 6 remained mice from each group. The degree of kidney fibrosis was observed through sirus red staining. Results Compared with those in sham group, tubular interstitial damage was aggravated (P＜0.05), BUN and Scr were increased (P＜0.05), the mRNA expression of IL-1β, IL-6 and TNF-α was increased at the 2 d after operation (all P＜0.05), and the level of AMPK phosphorylation was activated in IRI group and NS/IRI group (all P＜0.05); the degree of kidney fibrosis and the expression of COL1, α-SMA and FN were increased obviously at the 14 d (all P＜0.05). Compared with those in IRI group, in AMPK/IRI group tubular interstitial damage was aggravated (P＜0.05), BUN and Scr were increased (all P＜0.05), the mRNA expression of IL-1β, IL-6 and TNF-α was increased at the 2 d (all P＜0.05), and the level of AMPK phosphorylation was decreased (P＜0.05). Moreover, the degree of kidney fibrosis and the expression of COL1, α-SMA and FN were increased obviously at the 14 d in AMPK/IRI group (all P＜0.05). Conclusions AMPK can ameliorate the acute renal ischemia reperfusion injury induce fibrosis in mice, and the mechanism may be related to the decrease of inflammatory reaction.     

1型血管紧张素Ⅱ受体拮抗剂抑制大鼠胰腺纤维化形成

目的探讨1型血管紧张素Ⅱ受体(AT1)拮抗剂洛沙坦对大鼠实验性胰腺纤维化形成的抑制作用。方法胰管内注射2％三硝基苯磺酸(TNBS)诱导大鼠胰腺纤维化模型。于制模后第2天，治疗组给予洛沙坦(10mg／kg体重)灌胃，每日1次，对照组给予等容积的无菌蒸馏水。于制模后3，7，14，21．28d分别处死两组大鼠(每时点各6只)，并留取血清和胰腺组织。通过HE染色和Van Gieson(V-G)染色观察胰腺组织病理学改变和细胞外基质胶原纤维分布。分别应用放射免疫法和酶动力法测定血清透明质酸(HA)和淀粉酶。胰腺组织AT1受体蛋白和mRNA表达分别采用免疫组化和逆转录-聚合酶链式反应(RT-PCR)方法。结果洛沙坦可抑制TNBS诱导的大鼠胰腺纤维化形成，降低胰腺组织炎症细胞浸润、腺泡细胞坏死及纤维化程度，并且能降低血清HA和淀粉酶水平、下调AT1受体基因和蛋白的表达。结论1型血管紧张素Ⅱ受体拮抗剂对TNBS诱导的大鼠胰腺纤维化形成具有抑制作用，表明肾素-血管紧张素系统(RAS)在慢性胰腺炎胰腺纤维化的发生发展过程中起重要的介导调节作用。     

Effects of Ligustrazine on pulmonary damage in rats following scald injury

Organ protection is a routine therapy in severe burn/scald injuries, and damage mechanisms following early scald injury was not been fully elucidated. Our aim was to verify the beneficial effects of Ligustrazine on pulmonary damage associated with scald injury. Lewis rats were subjected to 30% total body surface area (TBSA) scald injury, and were randomly divided into a burn control (S group) and an Ligustrazine-treated group (L group). Lung malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined and the lungs were examined histologically with immunohistochemistry (IHC) as well for the MHC class I chain-related antigen A (MICA) and Bcl-2 at 24, 48 and 72h after the injury. The expression of spleen HLA-DR was detected by immunohistochemistry analysis. Selectins and adhesion molecules in lungs and serum as well as pulmonary interleukins were also detected. The lung injury degree was represented as wet/dry (W/D) values and alveolar thickness. Ligustrazine decreased MDA levels and ameliorated the down-regulation of SOD activity. MICA was up-regulated after the scald, and this up-regulation was greatly diminished by Ligustrazine. Bcl-2 was up-regulated after the scald, especially in the L group. The spleen HLA-DR expression demonstrated the immunoregulatory effects of Ligustrazine, which effectively protected pulmonary tissues from scald-induced injury. Our results demonstrated that pulmonay damage associated with autoimmunity and oxidant attack occurred after severe scald. Ligustrazine exhibits significant protective effects on these effects.     

生酮饮食对幼鼠颅脑损伤后继发性脑损伤的保护作用

目的 观察生酮饮食对幼鼠颅脑损伤后继发性脑损伤的保护作用.方法 应用Feeney自由落体模型制造局灶性脑挫伤,外伤后予正常饮食或生酮饮食.外伤后72 h,干湿重法测量脑水肿,Western blot法检测胞质及线粒体内细胞色素C(Cytc)含量,TUNEL法检测半暗区神经细胞凋亡.结果 颅脑损伤后,和正常饮食组大鼠比较,接受生酮饮食的大鼠脑水肿(81.2%比80.7%)、Cytc释放(1.46比0.62)及细胞凋亡(24.3%比17.0%)均明显减轻.结论 生酮饮食对颅脑损伤后继发性损伤具有治疗作用.