FGFR3在大鼠肝硬化模型中的动态表达研究

目的：观察大鼠肝硬化形成过程中成纤维细胞生长因子受体3（Fibroblast growth factor receptor3,FGFR3）的表达变化。方法：70只雄性SD大鼠,随机取10只作为对照组,其余60只作为肝硬化组。采用剂量频次渐变式四氯化碳（CCL）腹腔内注射建立肝硬化大鼠模型。检测2组大鼠的血清ALT、体重、肝体比,病理组织行包括HE和嗜银染色．并采用荧光定量聚合酶链反应（real—timePCR）和蛋白质印迹（Western blot）检测FGFR3基因和相应蛋白在肝硬化形成过程中的表达变化。结果：肝硬化组大鼠的血清ALT、肝体比和死亡率均显著高于对照组（P均〈0．01）;而体重则显著低于对照组（P〈0．01）;肝硬化组大鼠肝组织大体观察、HE染色及嗜银染色均呈明显肝硬化表现,而对照组则无该表现：real-timePCR及Western-blot结果显示,FGFR3在肝硬化形成过程中总体表达逐渐增强。结论：剂量频次渐变式GEl4腹腔内注射法是一种高效、低成本的大鼠肝硬化建模方法。而肝组织FGFR3在肝硬化发生、发展过程中的动态表达在一定程度上反映了肝纤维化及肝硬化程度。     

A Mouse Mammary Gland Involution mRNA Signature Identifies Biological Pathways Potentially Associated with Breast Cancer Metastasis

Mouse mammary gland involution resembles a wound healing response with suppressed inflammation. Wound healing and inflammation are also associated with tumour development, and a ‘wound-healing’ gene expression signature can predict metastasis formation and survival. Recent studies have shown that an involuting mammary gland stroma can promote metastasis. It could therefore be hypothesised that gene expression signatures from an involuting mouse mammary gland may provide new insights into the physiological pathways that promote breast cancer progression. Indeed, using the HOPACH clustering method, the human orthologues of genes that were differentially regulated at day 3 of mammary gland involution and showed prolonged expression throughout the first 4 days of involution distinguished breast cancers in the NKI 295 breast cancer dataset with low and high metastatic activity. Most strikingly, genes associated with copper ion homeostasis and with HIF-1 promoter binding sites were the most over-represented, linking this signature to hypoxia. Further, six out of the ten mRNAs with strongest up-regulation in cancers with poor survival code for secreted factors, identifying potential candidates that may be involved in stromal/matrix-enhanced metastasis formation/breast cancer development. This method therefore identified biological processes that occur during mammary gland involution, which may be critical in promoting breast cancer metastasis that could form a basis for future investigation, and supports a role for copper in breast cancer development. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. An erratum to this article can be found at     

苦参素对实验性肝纤维化的干预作用

目的:观察苦参素对四氯化碳(CCl4)诱导的实验性肝纤维化的干预作用。方法:将SD大鼠分成正常对照组、模型组、苦参素小剂量治疗组(40mg/kg)、中剂量治疗组(80mg/kg)、大剂量治疗组(160mg/kg),造模4周后苦参素治疗至实验第10周,取血测相关血清学指标,计算肝脏指数,测定肝组织匀浆中HYP和MDA含量。结果:苦参素能降低肝纤维化大鼠血清丙转氨酶(ALT)、谷草转氨酶(AST)、胆汁酸(TBA)、γ-谷氨酰转移酶(GGT)和肝脏指数,同时能减少肝组织中羟脯氨酸(HYP)和MDA含量(P<0.05或P<0.01)。结论:苦参素具有抗CCl4诱导的实验性肝纤维化的作用。     

灵芝孢子粉对四氯化碳致大鼠肝硬化的干预作用

目的：观察灵芝孢子粉对肝硬化大鼠脏器指数及肝组织形态的影响。方法：80只健康SD大鼠被随机均分为4组．即空白对照组、模型组、灵芝孢子粉低剂量组、灵芝孢子粉高剂量组。除空白对照组不做处理外,其他各组采用四氯化碳菜籽油溶液复制模型,模型复制同时灌胃给予灵芝孢子粉混悬液,连续8周后测量肝脾湿质量,取肝左叶制备切片用于苏木精-伊红染色。结果：①与空白对照组比较,模型组体质量显著降低（P〈0．05）,肝湿质量、肝指数、脾指数显著增加（P〈0．05）;与模型组比较,灵芝孢子粉低、高剂量组肝指数显著降低（P〈0．05）。②与模型组比较,灵芝孢子粉低、高剂量组肝脏汇管区有少量纤维组织增生,但未见假小叶结构。结论：灵芝孢子粉可以抑制四氯化碳对大鼠肝纤维化的作用。     

Salvinorin A inhibits colonic transit and neurogenic ion transport in mice by activating κ-opioid and cannabinoid receptors

Abstract  The major active ingredient of the plant Salvia divinorum , salvinorin A (SA) has been used to treat gastrointestinal (GI) symptoms. As the action of SA on the regulation of colonic function is unknown, our aim was to examine the effects of SA on mouse colonic motility and secretion in vitro and in vivo . The effects of SA on GI motility were studied using isolated preparations of colon, which were compared with preparations from stomach and ileum. Colonic epithelial ion transport was evaluated using Ussing chambers. Additionally, we studied GI motility in vivo by measuring colonic propulsion, gastric emptying, and upper GI transit. Salvinorin A inhibited contractions of the mouse colon, stomach, and ileum in vitro , prolonged colonic propulsion and slowed upper GI transit in vivo . Salvinorin A had no effect on gastric emptying in vivo . Salvinorin A reduced veratridine-, but not forskolin-induced epithelial ion transport. The effects of SA on colonic motility in vitro were mediated by κ-opioid receptors (KORs) and cannabinoid (CB) receptors, as they were inhibited by the antagonists nor-binaltorphimine (KOR), AM 251 (CB₁ receptor) and AM 630 (CB₂ receptor). However, in the colon in vivo , the effects were largely mediated by KORs. The effects of SA on veratridine-mediated epithelial ion transport were inhibited by nor-binaltorphimine and AM 630. Salvinorin A slows colonic motility in vitro and in vivo and influences neurogenic ion transport. Due to its specific regional action, SA or its derivatives may be useful drugs in the treatment of lower GI disorders associated with increased GI transit and diarrhoea.     

Physiology and pathobiology of the pericyte-containing retinal microvasculature: new developments

Evidence is accumulating that pericyte-containing microvessels, which constitute the largest component of the circulatory system, actively regulate capillary perfusion. Because the retinal vasculature is highly specialized for the local control of blood flow, experimental study of its microvessels is proving useful in the quest to elucidate the mechanisms by which local perfusion is regulated. The microcirculation of the retina is also a focus of considerable attention due to its vulnerability to diabetes, which is a leading cause of vision loss. Based on the premise that the transmembrane movement of ions plays a critical role in regulating the function of pericytes, investigators are using the patch-clamp technique to study these contractile mural cells. This review highlights recent progress made in understanding how ion channels and transporters mediate responses of the retinal microvasculature to vasoactive signals.     

Basilar artery blood flow velocity changes in patients with panic disorder following 35% carbon dioxide challenge

PURPOSE: We compared the mean basilar artery blood flow velocity (BABFV) between patients with panic disorder and healthy subjects both at rest and immediately following carbon dioxide (CO(2)) challenge, and examined the effects of treatment on BABFV. METHODS: Twenty four patients with panic disorder with or without agoraphobia and 12 healthy comparison subjects were studied. Visual Analog Anxiety Scale was used to evaluate the anxiogenic effect of 35% CO(2) inhalation. Mean BABFV was monitored using transcranial Doppler ultrasonography at rest and 10, 20, 30, 60, 90, 120 s after 35% CO(2) challenge both before and after four weeks treatment with paroxetine. RESULTS: The hemodynamic response pattern of basilar artery to CO(2) inhalation was significantly different between two groups. CO(2) rapidly triggered blood flow velocity in basilar artery amongst panic patients but not in healthy comparisons. The mean time to normalization of BABFV was significantly longer in panic patients. Four weeks of treatment with paroxetine led to a significantly reduced mean BABFV after 35% CO(2) inhalation in comparison with pretreatment. CONCLUSIONS: Patients with panic disorder had impaired cerebral regulatory mechanisms observed as a change in response characteristics in BABFV in response to CO(2) inhalation. Treatment with paroxetine reduced the increase of BABFV seen in patients after the CO(2) challenge.     

Cross-talking between 5-HT3 and GABAA receptors in cultured myenteric neurons

We recorded whole-cell ion currents induced by gamma-aminobutyric acid (I(GABA)) and serotonin (I(5-HT)) to investigate and characterize putative interactions between GABA(A) and 5-HT(3) receptors in myenteric neurons from the guinea pig small intestine. I(GABA) and I(5-HT) were inhibited by bicuculline and ondansetron, respectively. Currents induced by the simultaneous application of both, GABA and 5-HT (I(GABA+5-HT)) were significantly lower than the sum of I(GABA) and I(5-HT), indicating the existence of a current occlusion. Such an occlusion was observed when GABA(A) and 5-HT(3) receptors are virtually saturated. Kinetics, and pharmacological properties of I(GABA+5-HT) indicate that they are mediated by activation of both, GABA(A) and 5-HT(3) channels. GABA did not alter I(5-HT) in neurons without GABA(A) channels, in the presence of bicuculline (a GABA(A) receptor antagonist) or at the reversal potential for I(GABA). Similarly, 5-HT did not modify I(GABA) in neurons in which 5-HT(3) channels were absent, after inhibiting 5-HT(3) channels with ondansetron (a 5-HT(3) receptor antagonist) or at the reversal potential for I(5-HT). Current occlusion was observed as soon as GABA(A) and 5-HT(3) channels were being activated, in the absence of Ca(2+), at low temperature (11 degrees C), and after adding staurosporine (a protein kinase inhibitor) to the pipette solution. Our proposal is that GABA(A) and 5-HT(3) channels are organized in clusters and within these, both channels can cross-inhibit each other, likely by allosteric interactions between these proteins.     

肝舒胶囊对急性肝损伤动物的保护作用

目的 研究肝舒胶囊对大、小鼠急性肝损伤的保护作用.方法 采用皮下注射四氯化碳(CCl_4)诱导小鼠产生急性肝损伤模型,测定血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸基转移酶(AST)、总胆红素(TBIL)的含量和肝指数;腹腔注射D-氨基半乳糖胺盐酸盐(D-Gal)致大、小鼠急性肝损伤模型,测定血清中ALT、AST、ALP的含量及对肝指数的影响.结果 肝舒胶囊对CCl_4致小鼠急性肝损伤血清中的ALT、AST、TBIL升高有一定的抑制作用,但无统计学差异;肝舒胶囊高、中剂量能显著降低D-Gal致急性肝损伤小鼠血清中ALT、AST、ALP的含量,中剂量(0.95 g·kg~(-1))能显著降低D-Gal致急性肝损伤大鼠血清中ALT、AST的含量.结论 肝舒胶囊对化学性急性肝损伤有一定的保护作用.