Effect of the implant composite of poly lactide-co-glycolide and bone mesenchymal stem cells modified by basic fibroblast growth factor on injured spinal cord in rats

Objective To investigate the effect of the implant composite of poly lactide-co-glycolide(PLGA)and bone mesenchymal stem cells (BMSCs) modified by basic fibroblast growth factor (bFGF) on injured spinal cord in rats.Methods Two hundred and

Effect of charge at an amino acid of basic fibroblast growth factor on its mitogenic activity

The amino acid at the 119th position of human basic fibroblast growth factor(hbFGF),lysine(K119),is a critical component for its mitogenic activity.However,little is known about the effects of the characteristics of this residue including charge on the mitogenic activity of hbFGF.Herein,this basic residue was replaced with neutral glutamine residue and acidic glutamic acid residue to construct mutants hbFGF^(K119Q) and hbFGF^(K119E),respectively.The mutants were produced by BL21(DE3)/pET3c expression system...

Basic fibroblast growth factor increases the numbe of endogenous neural stem cells and inhibits the expression of amino methyl isoxazole propionic acid receptors in amyotrophic lateral sclerosis mice

This study aimed to investigate the number of amino methyl isoxazole propionic acid （AMPA） receptors and production of endogenous neural stem cells in the SOD1 G93AG1H transgenic mouse model of amyotrophic lateral sclerosis, at postnatal day 60 following administration of basic fibroblast growth factor （FGF-2）. A radioligand binding assay and immunohistochemistry were used to estimate the number of AMPA receptors and endogenous neural stem cells respectively. Results showed that the number of AMPA receptors and endogenous neural stem cells in the brain stem and sensorimotor cortex were significantly increased, while motor function was significantly decreased at postnatal days 90 and 120. After administration of FGF-2 into mice, numbers of endogenous neural stem cells increased, while expression of AMPA receptors decreased, whilst motor functions were recovered. At postnatal day 120, the number of AMPA receptors was negatively correlated with the number of endogenous neural stem cells in model mice and FGF-2-treated mice. Our experimental findings indicate that FGF-2 can inhibit AMPA receptors and increase the number of endogenous neural stem cells, thus repairing neural injury in amyotrophic lateral sclerosis mice.

Exogenous acid fibroblast growth factor inhibits ischemia-reperfusion-induced damage in intestinal epithelium via regulating P53 and P21WAF-1 expression

AIM： To detect the effect of acid fibroblast growth factor （aFGF） on P53 and P21WAF-1 expression in rat intestine after ischemia-reperfusion （I-R） injury in order to explore the protective mechanisms of aFGF. METHODS： Hale rats were randomly divided into four groups, namely intestinal ischemia-reperfusion group （R）, aFGF treatment group （A）, intestinal ischemia group （I）, and sham-operated control group （C）. In group I, the animals were killed after 45 min of superior mesenteric artery （SHA） occlusion. In groups R and A, the rats sustained for 45 min of SHA occlusion and were treated with normal saline （0.15 mL） and aFGF （20 μg/kg, 0.15 mL）, then sustained at various times for up to 48 h after reperfusion. In group C, SHA was separated, but without occlusion. Apoptosis in intestinal villi was determined with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling technique （TUNEL）. Intestinal tissue samples were taken not only for RT- PCR to detect P53 and P21WAF-1 gene expression, but also for immunohistochemical analysis to detect P53 and P21WAF-1 protein expression and distribution. RESULTS： In histopathological study, ameliorated intestinal structures were observed at 2, 6, and 12 h after reperfusion in A group compared to R group. The apoptotic rates were （41.17±3.49）%, （42.83±5.23）%, and （53.33±6.92）% at 2, 6, and 12 h after reperfusion, respectively in A group, which were apparently lower than those in R group at their matched time points （50.67±6.95）%, （54.17±7.86）%, and （64.33±6.47）%, respectively, （P〈0.05））. The protein contents of P53 and P21WAF-1 were both significantly decreased in A group compared to R group （P〈0.05） at 2-12 h after reperfusion, while the mRNA levels of P53 and P21VVAF-1 in A group were obviously lower than those in R group at 6-12 h after reperfusion （P〈0.05）. CONCLUSION： P53 and P21WAF-1 protein accumulations are associated with intestinal barrier injury induced by I-R insult, while intravenous aFGF can alleviate apoptosis of rat intestinal cells by inhibiting P53 and P21WAF-1 protein expression.

Fibroblast growth factor 15,induced by elevated bile acids,mediates the improvement of hepatic glucose metabolism after sleeve gastrectomy

BACKGROUND Fibroblast growth factor(FGF)15/19,which is expressed in and secreted from the distal ileum,can regulate hepatic glucose metabolism in an endocrine manner.The levels of both bile acids(BAs)and FGF15/19 are elevated after bariatric surgery.However,it is unclear whether the increase in FGF15/19 is induced by BAs.Moreover,it remains to be understood whether FGF15/19 elevations contribute to improvements in hepatic glucose metabolism after bariatric surgery.AIM To investigate the mechanism of improvement of hepatic glucose metabolism by elevated BAs after sleeve gastrectomy(SG).METHODS By calculating and comparing the changes of body weight after SG with SHAM group,we examined the weight-loss effect of SG.The oral glucose tolerance test(OGTT)test and area under the curve of OGTT curves were used to assess the anti-diabetic effects of SG.By detecting the glycogen content,expression and activity of glycogen synthase as well as the glucose-6-phosphatase(G6Pase)and phosphoenolpyruvate carboxykinase(Pepck),we evaluated the hepatic glycogen content and gluconeogenesis activity.We examined the levels of total BA(TBA)together with the farnesoid X receptor(FXR)-agonistic BA subspecies in systemic serum and portal vein at week 12 post-surgery.Then the histological expression of ileal FXR and FGF15 and hepatic FGF receptor 4(FGFR4)with its corresponding signal pathways involved in glucose metabolism were detected.RESULTS After surgery,food intake and body weight gain of SG group was decreased compare with the SHAM group.The hepatic glycogen content and glycogen synthase activity was significantly stimulated after SG,while the expression of the key enzyme for hepatic gluconeogenesis:G6Pase and Pepck,were depressed.TBA levels in serum and portal vein were both elevated after SG,the FXR-agonistic BA subspecies:Chenodeoxycholic acid(CDCA),lithocholic acid(LCA)in serum and CDCA,DCA,LCA in portal vein were all higher in SG group than that in SHAM group.Consequently,the ileal expression of FXR and FGF15 were also advanced in SG group.Moreover,the hepatic expression of FGFR4 was stimulated in SG-operated rats.As a result,the activity of its corresponding pathway for glycogen synthesis:FGFR4-Ras-extracellular signal regulated kinase pathway was stimulated,while the corresponding pathway for hepatic gluconeogenesis:FGFR4-cAMP regulatory element-binding protein-peroxisome proliferator-activated receptorγcoactivator-1αpathway was suppressed.CONCLUSION Elevated BAs after SG induced FGF15 expression in distal ileum by activating their receptor FXR.Furthermore,the promoted FGF15 partly mediated the improving effects on hepatic glucose metabolism of SG.

Role of Fibroblast Growth Factor 19 in Maintaining Nutrient Homeostasis and Disease

Fibroblast growth factor 19 （FGF19） is a kind of gut-derived postprandial hormone. As an atypical member of the FGF family, FGF19 functions as an endocrine hormone except regulating cell growth and differentiation. FGF19 plays a key role in coordination of liver bile acid biosynthesis and gallbladder motility, and acts as a regulator of metabolic homeostasis, including strengthening insulin sensitivity, decreasing triglyceride concentration and reducing body weight.

Effect of basic fibroblast growth factor on cat corneal endothelial cell proliferation

AIM: To investigate the function of basic fibroblast growth factor (bFGF) on cat corneal endothelial cells proliferation. METHODS: Cat corneal endothelial cells were primarily cultured, stimulated with bFGF for different period, the proliferation of cells was assayed by modified tertrozalium salt (MTT) method, and the morphologic changes were observed with inverted phase contrast microscope and transmission electron microscope. RESULTS: At 1, 3 and 5 days after bFGF was added to cat corneal endothelial cells, the result of MTT in 490nm showed significant difference than that in control group, and the difference was most significant in 10ng/mL group. CONCLUSION: bFGF can promote proliferation of cat corneal endothelial cells. 10ng/mL is the relatively most effective dose.

The change of basic fibroblast growth factor and effect of prostacyclin in lung injury

In this study,the changes in activity and mRNA transcript of basic fibroblast growth fac-tor(bFGF)in lung injury and the effect of prostacyclin on the treatment of lung injury wereinvestigated.The result of the experiment revealed that there were not any bioactive bFGF andbFGF mRNA in the lung tissue of normal dogs.bFGF activity and bFGF mRNA were detectedonly in the injured lung tissue.Prostacyclin could slightly elevate the activity of bFGF andsignificantly elevate the level of bFGF mRNA.The findings suggest that(1)the level of bFGF in-creased after lung injury.(2)Prostacyclin could influence the expression of bFGF.(3)bFGF couldplay an important role in the repair of injury lung tissue.

ACIDIC FIBROBLAST GROWTH FACTOR REDUCES RAT SKELETAL MUSCLE DAMAGE CAUSED BY ISCHEMIA AND REPERFUSION

Acute interruption of arterial blood flow to the extremities is often associated with significant morbidity and mortality. Broad spectrum mitogenic and non mitogenic activities of FGFs inspired us to study its protecting effects on tissue injuries in ischemia reperfusion condition. We found that systemic administration of aFGF after reperfusion onset prevented severe skeletal muscle injuries. In rats treated with aKGF, the tissue edema was reduced significantly, the tissue viability was increased, and the muscle fibers contained more succinate dehydrogenase (SDH) and adenosine triphosphatasc (ATPase). The pathological results supported the concept of improved prevention with aFGF treatment. The possible tissue protection by aFGF may come from its ability to regulate the concentration of evtra- and intracellular calcium ion. Besides, it may moderate other Ca2+ dependent enzyme conversion processes. Also, it may take part in the vascular tone regulation under ischemia and reperfusion conditions. These results suggest further study of tissue ischemia prevention with FGF and its possible mechanisms in the future.

Effect of basic fibroblast growth factor on the expression of glial fibrillary acidic protein after tractive spinal cord injury in rats

OBJECTIVE: To investigate the effects of basic fibroblast growth factor (bFGF) on the expression of glial fibrillary acidic protein (GFAP) after tractive spinal cord injury in rats and to explore the recovery of spinal cord function. METHODS: The rats were subjected to tractive spinal cord injury at T13-L2. Cortical somatosensory-evoked potential (CSEP) was closely monitored and when P1-N1 wave amplitude decreased to 70% of that before operation, a small-bore catheter was inserted below the injured plane through subarachnoid cavity. In the treatment groups, 20 microl of bFGF solution (containing 20 microg of bFGF) was injected through the catheter right after the operation and 1, 2, 3, 4, 8, 12 and 24 h postoperatively. In the control group, same volume of normal saline was injected and every four rats were killed at 1, 4, 7, 14 and 21 d after the operation. Combined behavior score (CBS) and electro-physiological examination were adopted to evaluate function recovery. Expression of GFAP was observed by immuno-histochemical staining and was analyzed quantitatively by computer image analysis. RESULTS: There was statistically significant difference in GFAP-positive cells between bFGF treatment group and the control group (P

maFGF对慢性衰老大鼠肝组织中ATP酶活力的影响

目的观察改构型酸性成纤维细胞生长因子(maFGF)对D-半乳糖致衰老大鼠肝组织中Na+-K+-ATP酶活力及Ca2+-Mg2+-ATP酶活力的影响,探讨maFGF抗衰老的机制。方法选择成年Wistar大鼠40只,采用皮下注射D-半乳糖建立衰老模型,衰老模型成功后随机分为衰老对照组、NS对照组和maFGF治疗组各10只。另10只不注射D-半乳糖作为正常对照组。maFGF治疗组按12μg/kg剂量肌肉注射ma FGF,1次/d,共14 d,NS对照组肌肉注射与maFGF治疗组相同容量的生理盐水,1次/d;衰老对照组不作任何干预。各组大鼠到相对应的时间点取出各组大鼠肝组织,测定肝组织匀浆中Na+-K+-ATP酶活力及Ca2+-Mg2+-ATP酶活力。结果与正常对照组相比,衰老对照组大鼠肝组织中Na+-K+-ATP酶活力及Ca2+-Mg2+-ATP酶活力均明显降低(P<0.01);maFGF治疗组肝组织中Na+-K+-ATP酶活力和Ca2+-Mg2+-ATP酶活力均明显高于衰老对照组、NS对照组(P<0.05)。结论 maFGF能升高衰老大鼠肝组织中Na+-K+-ATP酶活力及Ca2+-Mg2+-ATP酶活力,对衰老大鼠肝损伤有一定保护作用。

maFGF对衰老大鼠脑组织SOD、MDA和羟自由基及神经细胞凋亡的影响

目的观察改构型酸性成纤维细胞生长因子(maFGF)对D-半乳糖致衰老大鼠脑组织SOD活力、MDA含量和羟自由基含量及神经细胞凋亡的影响,探讨maFGF对慢性衰老大鼠的抗衰老作用。方法选择成年Wistar大鼠48只,采用皮下注射D-半乳糖建立衰老模型,衰老模型成功后随机分为衰老模型组、生理盐水(NS)对照组和maFGF治疗组。另16只不注射D-半乳糖作为正常对照组。各组大鼠到相对应的时间点取出脑组织,测定脑组织中SOD活力、MDA含量和抑制羟自由基能力;TUNEL法测定大鼠大脑皮质神经细胞凋亡数目。结果衰老模型组大鼠脑组织SOD活力显著降低,MDA含量和羟自由基含量升高,皮质神经细胞凋亡数明显增多;经过用maFGF治疗慢性衰老大鼠后脑组织SOD活力显著升高,MDA含量和羟自由基含量均显著降低,皮质神经细胞凋亡数明显减少。结论 maFGF起到降低自由基,提高脑组织的抗氧化能力,减少皮质神经细胞凋亡数量。

maFGF对慢性衰老大鼠自由基代谢的影响

目的观察改构型酸性成纤维细胞生长因子(maFGF)对D-半乳糖致衰老大鼠肝组织丙二醛(MDA)含量、超氧化物歧化酶(SOD)活力和羟自由基含量的影响,探讨maFGF对慢性衰老大鼠的抗衰老作用。方法选择成年Wistar大鼠30只,采用皮下注射D-半乳糖建立衰老模型,衰老模型成功后随机分为衰老对照组、生理盐水(NS)对照组和maFGF治疗组。另10只不注射D-半乳糖作为正常对照组。maFGF治疗组按12g/kg剂量肌肉注射,1次/d,共14d,NS对照组肌肉注射与maFGF治疗组相同容量的生理盐水,1次/d;衰老对照组不作任何干预。各组大鼠到相对应的时间点取出各组大鼠肝组织,测定肝组织匀浆MDA含量、SOD活力和抑制羟自由基能力。结果衰老对照组大鼠肝组织MDA含量显著升高,SOD活力显著降低,羟自由基含量升高;经过用maFGF治疗慢性衰老大鼠后肝组织MDA含量明显降低,SOD活力显著升高,羟自由基含量显著降低。结论 maFGF起到降低自由基,提高肝组织的抗氧化能力,对细胞具有保护作用。

maFGF对慢性衰老大鼠脑组织中ATP酶活力的影响

目的观察改构型酸性成纤维细胞生长因子(maFGF)对D-半乳糖致衰老大鼠脑组织中Na+-K+-ATP酶活力及Ca2+-Mg2+-ATP酶活力的影响,探讨maFGF抗衰老的机制。方法选择成年Wistar大鼠40只,采用皮下注射D-半乳糖建立衰老模型,衰老模型成功后随机分为衰老对照组、NS对照组和maFGF治疗组。另10只不注射D-半乳糖作为正常对照组。maFGF治疗组按12μg/kg剂量肌内注射,1次/d,共14 d,NS对照组肌肉注射与maFGF治疗组相同容量的生理盐水,1次/d;衰老对照组不作任何干预。各组大鼠到相对应的时间点取出各组大鼠脑组织,测定脑组织匀浆中Na+-K+-ATP酶活力及Ca2+-Mg2+-ATP酶活力。结果与正常对照组相比,衰老对照组大鼠脑组织中Na+-K+-ATP酶活力及Ca2+-Mg2+-ATP酶活力均明显著降低(P<0.01);maFGF治疗组脑组织中Na+-K+-ATP酶活力和Ca2+-Mg2+-ATP酶活力均明显高于衰老对照组、NS对照组(P<0.05)。结论 maFGF能升高衰老大鼠脑组织中Na+-K+-ATP酶活力及Ca2+-Mg2+-ATP酶活力,对衰老大鼠脑损伤有一定保护作用。

MaFGF对慢性脑缺血再灌注损伤小鼠神经功能保护的机制研究

目的探讨改构型酸性成纤维细胞生长因子(MaFGF)对慢性脑缺血再灌注损伤小鼠神经保护的可能机制。方法将24只雄性C57BL/6J小鼠按随机数字表法分为Sham组、BCAO组和BCAO+MaFGF组,每组各8只。建模完成后,BCAO+MaFGF组鼻内给药MaFGF20μg/(kg.d),其余2组给予相同体积的生理盐水。采用mNSS评估小鼠神经功能损害程度,通过Morris水迷宫试验评估小鼠的学习记忆能力,Nissl染色法观察小鼠海马CA1区神经元细胞的形态结构学改变,Western biot法检测小鼠海马区p-PI3K、p-AKT、GRP170、CHOP、caspase-12蛋白表达水平,免疫荧光染色法观察小鼠海马CA1区神经元p-AKT、GRP170的表达情况。结果与Sham组比较,BCAO组小鼠mNSS评分明显升高(P<0.05),学习记忆能力下降(P<0.05),BCAO组小鼠海马CA1区神经元细胞结构破坏明显,坏死细胞数目明显增多(P<0.05),其海马区CHOP和caspase-12明显升高(P<0.05),而p-PI3K、p-AKT、GRPI70均未见明显改变(P>0.05);与:BCAO组比较,BCAO+MaFGF组小鼠mNSS评分明显降低(P<0.05),学习记忆能力上升(P<0.05),BCAO组小鼠海马CA1区神经元细胞结构较为完整,排列整齐,坏死细胞数目明显减少(P<0.05),其海马区CHOP和caspase-12表达明显降低(P<0.05),而p-PI3K、p-AKT、GRP170表达明显升高(P<0.05)。结论MaFGF能够改善慢性脑缺血再灌注损伤小鼠的神经功能,其可能机制是通过激活PI3K/AKT信号通路,减轻内质网应激,减少细胞凋亡而起神经保护作用。

超声微泡靶向递送MaFGF改善糖尿病心肌病大鼠左心室收缩功能的初步实验研究

目的探讨应用超声靶向微泡击破技术(UTMD)递送改构型酸性成纤维细胞生长因子(MaFGF)对改善糖尿病心肌病(DCM)大鼠的左心室收缩功能的价值。方法将75只健康雄性SD大鼠适应性饲养1周后,采用随机数字表法挑选15只作为正常对照组(N组),不做干预,余60只经腹腔注射链脲佐菌素(STZ)建立Ⅰ型糖尿病模型(70mg/kg),将造模成功52只大鼠继续饲养8周,继而采用随机数字表法分为4组(DCM模型组、MaFGF组、MaFGF-SonoVue组及MaFGF-SonoVue+UTMD组,每组13只)。各组分别给予相应干预4周,然后对所有大鼠行常规超声心动图及速度向量成像(VVI)检查,测量并比较左心室舒张末期内径(LVIDd)、左心室收缩末期内径(LVIDs)、左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)、乳头肌水平左心室壁各节段平均径向峰值速度(Vs)、径向应变(Sr)及径向应变率(SRr)差异。随后处死大鼠取心肌组织,TUNEL染色计算心肌组织凋亡指数(AI),天狼星红染色计算心肌血管周围胶原面积与血管腔面积之比(PVCA/LA)。结果干预4周后,与N组比较,DCM组LVIDd及LVIDs均增加(均P<0.05),LVEF、LVFS、Vs、Sr及SRr均明显减低(均P <0.05),AI和PVCA/LA均明显升高(均P <0.05);与DCM组比较,MaFGF-SonoVue+UTMD组LVIDd及LVIDs均降低(均P<0.05);与DCM组及其他治疗组比较,MaFGF-SonoVue+UTMD组LVEF、LVFS、Vs、Sr及SRr均明显增高(均P<0.05),而AI、PVCA/LA均明显降低(均P<0.05)。结论应用UTMD技术递送MaFGF对改善DCM大鼠左心室收缩功能有重要价值,UTMD靶向传输系统可明显提高药效。

13-Methyltetradecanoic acid mitigates cerebral ischemia/reperfusion injury

13-Methyltetradecanoic acid can stabilize cell membrane and have anti-inflammatory, antioxidant and anti-apoptotic effects. Previous studies mainly focused on peripheral nerve injury, but seldom on the central nervous system. We investigated whether these properties of 13-methyltetradecanoic acid have a neuroprotective effect on focal cerebral ischemia/reperfusion injury, and detected the expression of basic fibroblast growth factor and vascular endothelial growth factor. This study established rat models of middle cerebral artery occlusion/ reperfusion injury by ischemia for 2 hours and reperfusion for 24 hours. At the beginning of reperfusion, 13-methyltetradecanoic acid 10, 40 or 80 mg/kg was injected into the tail vein. Results found that various doses of 13-methyltetradecanoic acid effectively reduced infarct volume, mitigate cerebral edema, and increased the mRNA and protein expression of basic fibroblast growth factor and vascular endothe- lial growth factor at 24 hours of reperfusion. The effect was most significant in the 13-methyltetradecanoic acid 40 and 80 mg/kg groups. The findings suggest that 13-methyltetradecanoic acid can relieve focal ischemia/reperfusion injury immediately after reperfusion, stimu- late the upregulation of basic fibroblast growth factor and vascular endothelial growth factor to exert neuroprotective effects.

超声微泡介导MaFGF对阿霉素心力衰竭大鼠心功能的保护作用及其机制研究

目的观察超声靶向微泡击破(UTMD)技术调控改构型酸性成纤维细胞生长因子(MaFGF)对阿霉素心力衰竭(HF)大鼠心功能的保护作用并探讨其机制。方法随机将40只实验动物(雄性健康SD大鼠)分为正常对照组、HF模型组、MaFGF组和MaFGF+UTMD组。后3组大鼠通过腹腔注入盐酸阿霉素,MaFGF+UTMD组大鼠经尾静脉注射内含MaFGF的超声微泡混悬液后心脏接受超声靶向微泡击破处理。经过6周干预,超声心动图检查测量左心室收缩末期内径(LVESd)、左心室舒张末期内径(LVEDd)、左心室短轴缩短率(LVFS)以及左心室射血分数(LVEF)。其后处死大鼠取心肌组织,检测心肌丙二醛(MDA)、超氧化物歧化酶(SOD)水平,通过Masson胶原染色计算心肌胶原容积分数(CVF)、血管周围胶原面积(PVCA)/血管腔面积(LA)比值,透射电镜下对心肌细胞超微结构进行观察。结果经过干预6周后,MaFGF+UTMD组LVESd及LVEDd较HF模型组减小(均P<0.05),LVEF、LVFS增高(均P<0.05);HF模型组心肌MDA较正常对照组升高,而SOD降低(均P<0.05),经过MaFGF+UTMD干预,MaFGF+UTMD组SOD上升而MDA降低(均P<0.05);Masson胶原染色显示与正常对照组比较HF模型组CVF与PVCA/LA增高(均P<0.05),而MaFGF+UTMD组这两项指标则下降(均P<0.05);透射电镜显示HF大鼠心脏结构明显异常且能量代谢紊乱,而由UTMD介导的MaFGF干预后,大鼠的心脏微观形态有所改善。结论对于由阿霉素诱导的心肌损伤,UTMD介导MaFGF对左心室收缩机能具有保护性,其机制可能与MaFGF缓解ROS损害心肌线粒体膜程度,抑制心肌纤维化的形成有关。

Lithocholic acid induction of the FGF19 promoter in intestinal cells is mediated by PXR

To study the effect of the toxic secondary bile acid lithocholic acid （LCA） on the expression of fibroblast growth factor 19 （FGF19） in intestinal cells and to characterize the pregnane-X-receptor （PXR） response of the FGF19 promoter region. METHODS： The intestinal cell line LS174T was stimulated with various concentrations of chenodeoxy- cholic acid and lithocholic acid for several time points. FGF19 mRNA levels were determined with quantitative realtime RT-PCR. FGF19 deletion promoter constructs were generated and the LCA response was analzyed in reporter assays. Co-transfections with PXR and RXR were carried out to study FGF19 regulation by these factors, RESULTS： LCA and CDCA strongly up-regulate FGF19 mRNA expression in LS174T cells in a time and dose dependent manner. Using reporter gene assays with several deletion constructs we found that the LCA responsive element in the human FGF19 promoter maps to the proximal regulatory region containing two poten- tial binding sites for PXR. Overexpression of PXR and its dimerization partner retinoid X receptor （RXR） and stimulation with LCA or the potent PXR ligand rifampicin leads to a significant induction of FGF19 promoter activ- ity in intestinal cells. CONCLUSION： LCA induced feedback inhibition of bile acid synthesis in the liver is likely to be regulated by PXR inducing intestinal FGF19 expression.

Effect of basic fibroblast growth factor and hyaluronic acid on proliferation of rabbit chondrocytes in vitro

Objective: To investigate the effect of basic fibroblast growth factor (bFGF) and hyaluronic acid (HA) on the proliferation of rabbit chondrocytes in vitro. Methods: Chondrocytes from the knee joints of New Zealand white rabbits were cultured. bFGF or HA or both were added into the culture medium respectively, and the proliferation of the chondrocytes was measured with MTT 3 (4, 5 dimethylthiazol 2 yl) 2, 5 diphenyl tetra zolium bromide. (MTT, Sigma, M2128). Results: Basic fibroblast growth factor (10 ng/ml) with low concentration of fetal bovine serum in the culture medium promoted the proliferation of chondrocytes significantly, and this effect reached its maximum when concentration of bFGF reached 50 ng/ml. HA itself had no effect on the proliferation of chondrocytes. However, when bFGF was used in combination with HA, especially when the concentration of bFGF was 50 500 ng/ml and that of HA was 10 50 ng/ml, the effect on the proliferation of chondrocytes was much more than when bFGF or HA was used alone. Conclusions: bFGF can promote the proliferation of chondrocytes. HA, which has no effect on the proliferation of the cells, can maintain a normal growth of chondrocytes. When bFGF is used in combination with HA, more proliferation is obtained.