左归丸对去卵巢大鼠股骨中Ⅰ型胶原mRNA表达的影响

目的观察左归丸对去卵巢骨质疏松(OP)模型大鼠股骨中Ⅰ型胶原mRNA表达的影响,探讨左归丸对OP的防治作用机制。方法SPF级4.5月龄SD雌性大鼠,分为三组:正常组39只;假手术组39只;200只采取双侧背部卵巢切除术进行绝经后OP造模。造模21 d后,将去卵巢大鼠随机分为5组:模型组、尼尔雌醇组、左归丸高剂量组、左归丸中剂量组、左归丸低剂量组,每组40只。然后开始灌胃给药,左归丸高、中、低剂量组分别给予ig6.4,3.2,1.6 g/kg剂量的左归丸混悬液灌胃;尼尔雌醇组灌服尼尔雌醇混悬液灌胃;正常组、假手术组和模型组均灌服蒸馏水。于连续给药60、120、180 d后分3批取材,取大鼠左后肢股骨近端1/3部分,采用RT-PCR方法检测骨组织中Ⅰ型胶原mRNA的表达水平。结果去卵巢后,与正常组比较,模型组大鼠股骨中Ⅰ型胶原mRNA水平明显降低(P<0.01);和模型组比较,给药60d、120、180 d的左归丸各剂量组,股骨中Ⅰ型胶原mRNA水平显著升高(P<0.01或P<0.05)。结论骨组织中Ⅰ型胶原的mRNA表达水平的下调可能是绝经后骨质疏松(PMOP)发生的重要机制之一,左归丸能够上调骨组织中Ⅰ型胶原的mRNA表达,从而有效防治OP。     

ⅩⅧ型胶原mRNA在实验性肝纤维化大鼠肝脏中的表达

目的了解XⅧ型胶原（collagenXⅧ,CXⅧ）mRNA在实验性肝纤维化中的定量改变。方法以逆行胆管硬化注射加结扎的方法制备大鼠胆管堵塞性肝纤维化模型,以假手术组大鼠为对照组。提取肝脏总RNA,以核酸酶保护分析（RNA酶保护分析）定量测定前胶原α1（XⅧ）mRNA水平,并与α1（Ⅰ）和金属蛋白酶组织抑制因子1（TIMP－1）的mRNA变化相比较。结果与假手术组大鼠相比,胆管堵塞性肝纤维化大鼠肝脏前胶原α1（Ⅰ）及TIMP－1mRNA水平分别升高20倍及4倍;而肝纤维化大鼠肝脏前胶原α1（XⅧ）mRNA水平仅升高到1.8倍。结论肝纤维化时肝脏XⅧ胶原仅轻度升高．这种变化类型可能和XⅧ胶原主要由肝实质细胞表达有关。     

替米沙坦对压力超负荷左心室肥厚大鼠心肌I型胶原代谢的影响

目的：探讨压力超负荷左心室肥厚大鼠I型胶原代谢特点及替米沙坦的干预效果。方法：24只雄性Spargue—Dawley大鼠随机分为假手术组（n=8）、左心室肥厚组（n=8）和替米沙坦组（n=8）。行腹主动脉缩窄术建立高血压左心室肥厚大鼠模型。各组干预4周后处死大鼠,称其体质量及左心室质量,计算左心室质量指数（LVMI）。将左心室心肌行Masson染剂染色,观察并测量其胶原容积分数（CVr）。用ELISA法检测3组大鼠血清I型前胶原羧基端肽（PICP）及I型胶原羧基端交联肽（ICTP）的浓度,并计算PICP／ICTP的比值,直线相关分析PICP及PICP／IC—TP比值与CVF的相关性。结果：与假手术组相比,左心室肥厚组左心室质量、LVMI、CVF、血清PICP及PICP／ICTP的比值均显著升高（均P〈0．05）;与左心室肥厚组相比,替米沙坦组左心室质量、LVMI、CVF、血清PICP、PICP／ICTP的比值均显著降低（均P〈0．05）。3组问的ICTP相比较,差异无统计学意义;PICP及PICP／ICTP比值均与CVF呈正相关（r值分别为0．830、0．842,均P〈0．01）。结论：压力超负荷左心室肥厚大鼠I型胶原合成增加、降解相对不足,合成与降解的不平衡是造成其左心室心肌间质纤维化的原因之一。替米沙坦可以抑制I型胶原的合成,纠正其合成与降解不平衡,从而有效地抑制及逆转心肌间质纤维化。     

雀啄回旋灸十二背俞穴对骨质疏松大鼠骨力学及骨代谢的影响

目的探讨雀啄回旋灸十二背俞穴对骨质疏松大鼠骨力学及骨代谢的影响。方法 8月龄未孕雌性大鼠50只,随机分成假手术组、模型组、艾灸组、艾灸加雌激素组、雌激素组。除假手术组外,其余均做摘卵巢手术。术后10 d(伤口愈合),依据组别不同分别施术(艾灸和雌激素治疗),90 d后对大鼠进行右侧股骨活体骨密度检测。处死后取大鼠右侧股骨、胫骨、肱骨进行骨力学检测(三点弯曲、拉伸、扭转);取血进行骨碱性磷酸酶检测;取尿液进行尿羟脯氨酸检测,其中尿羟脯氨酸在造模24 h后检测一次。结果在造模后24 h,摘卵巢各组比假手术组尿羟脯氨酸明显升高(P<0.05)。在艾灸与雌激素干预后,碱性磷酸酶、尿羟脯氨酸、骨力学比较分析,各干预组均优于模型组(P<0.05)。结论雀啄回旋灸十二背俞穴可有效阻止骨质疏松大鼠骨代谢的衰退,减缓骨力学的退变,可以作为延缓骨质疏松发生的一种中医康复保健手段。     

雌激素对SD大鼠血脂代谢的影响

目的探讨雌激素对SD大鼠血脂代谢的影响。方法24只12周龄雌性SD大鼠随机分为3组（1）去卵巢组（简称Ovx组），（2）去卵巢＋雌激素组（简称Ovx＋E2组），（3）假手术组，作为对照组。3月后断头取血，检测，血清雌二醇、血清总胆固醇、甘油三酯、高密度脂蛋白。结果去卵巢后的SD大鼠血清雌二醇水平明显低于假手术组，雌激素替代治疗后血清雌激素浓度明显升高，与假手术组相比没有明显差别。去卵巢组大鼠血清胆固醇水平明显高于假手术组，雌激素替代治疗后胆固醇水平降低，与假手术组相比无差异；大鼠去卵巢后血清甘油三酯稍有升高但没有统计学意义，去卵巢雌激素替代治疗组与假手术组相比较血清甘油三酯明显升高，与去卵巢组比较稍高，但没有统计学意义；去卵巢组大鼠血清高密度脂蛋白水平明显低于假手术组，给予雌激素替代治疗后血清高密度脂蛋白水平明显升高与假手术组没有明显的差别。结论雌激素替代治疗能调节SD大鼠的血脂代谢，降低胆固醇，升高高密度脂蛋白，但可使甘油三酯进一步升高。     

淫羊藿总黄酮对去卵巢大鼠骨组织Ⅰ型胶原代谢及组织蛋白酶K表达的影响

目的 观察淫羊藿总黄酮（HEF）对去卵巢大鼠骨组织中Ⅰ型胶原蛋白代谢及组织蛋白酶K表达的影响。方法 54只雌性SD大鼠随机分成6组。假手术组为阴性对照组，其余各组切除卵巢后分别不给予或给予HEF（每日40，80和160mg／kg）和尼尔雌醇（每日0．1mg／kg）治疗12周。测定大鼠全身骨密度和尿NTx／Cr比值，采用免疫组化法和Western印迹测定Ⅰ型胶原蛋白和组织蛋白酶K的含量。结果 12周后，HEF可以增加去卵巢大鼠的全身骨密度（均P〈0．05）。HEF各组Ⅰ型胶原的表达升高，组织蛋白酶K的表达及尿中NTX／Cr水平明显下降，并呈剂量依赖关系，以高剂量组最为显著（P〈0．01）。结论 HEF可能通过促进大鼠骨Ⅰ型胶原蛋白的合成、抑制其水解吸收从而提高大鼠骨密度，改善骨质量。     

低分子肝素联合依那普利对单侧输尿管梗阻大鼠肾组织结缔组织生长因子表达的影响

目的观察低分子肝素联合血管紧张素转换酶抑制剂依那普利对单侧输尿管梗阻大鼠肾组织结缔组织生长因子(CTGF)的影响。方法采用单侧输尿管梗阻模型,雄性SD大鼠40只随机分为假手术组、模型组、低分子肝素组、依那普利组和联合组,各8只。低分子肝素和依那普利组从造模前24 h开始分别以低分子肝素钙410 U/kg皮下注射每日2次、依那普利10 mg·kg-1·d-1灌胃,联合组给予上述2种治疗联用,模型组和假手术组以等体积的生理盐水皮下注射和灌胃。于造模后第14天处死大鼠,取梗阻侧肾组织,行HE染色和Masson染色观察各组大鼠肾组织病理改变,采用real-time PCR方法检测肾组织CTGF mRNA和Ⅰ型胶原mRNA的表达,应用Western印迹检测肾小管上皮细胞转分化标志CTGF蛋白表达。结果模型组大鼠肾间质损伤指数评分逐渐增加,肾间质胶原相对面积逐渐增大,CTGF mRNA、Ⅰ型胶原mRNA和CTGF蛋白表达增加。与模型组比较经低分子肝素、依那普利和二者联合治疗后,肾间质损伤指数和肾间质胶原相对面积下降,CTGF mRNA、Ⅰ型胶原mRNA和CTGF蛋白表达均减少(P<0.05),联合组优于两药单独治疗组比较(P<0.05),单独用药组组间比较无统计学意义(P>0.05)。结论低分子肝素和依那普利联合治疗可减轻梗阻侧肾间质纤维化程度,这一作用可能与抑制梗阻侧肾组织CTGF和I型胶原表达有关,低分子肝素和依那普利的单独用药效果不如联合治疗。     

降钙素治疗骨折的疗效观察及机制探讨

目的观察降钙素治疗骨折的疗效,并探讨其机制。方法选用64只2个月龄SD雌性大鼠,行双侧卵巢切除（OVX）后建立骨质疏松性骨折动物模型,随机分为观察组、对照组,各32只。观察组从骨折术前1周至术后8周每天皮下注射鲑鱼降钙素2IU／kg,对照组注射等量生理盐水。采用原位杂交技术检测7、14、28、56d骨痂中Ⅰ、Ⅱ、Ⅲ型胶原mRNA的表达。结果从骨折后第7天开始至第56天,各组Ⅲ型胶原mRNA表达水平逐渐下降,Ⅱ型胶原mRNA表达水平先升高后下降,Ⅰ型胶原mRNA表达水平逐渐升高。从第28天起,Ⅰ型胶原mRNA表达水平观察组〉对照组（P均〈0．05）。术后第56天观察组骨痂已为骨性,对照组可见较多软骨性骨痂。结论降钙索能促进软骨性骨痂向骨性骨痂转换,加速骨质疏松性骨折的愈合。其机制可能与降钙素能促进Ⅰ型胶原mRNA表达,抑制Ⅱ型胶原mRNA表达有关。     

18α甘草酸对I型胶原转录水平的调控

目的探讨18α甘草酸(18αGL)对CCl4诱导的肝纤维化大鼠的I型胶原的调控作用。方法采用40%CCl4皮下注射方法建立肝纤维化大鼠模型,分为正常组、肝纤维化模型组和18αGL干预组。采用免疫组织化学和实时PCR分析I型胶原表达情况。Signal-Net网络分析发现与I型胶原组分COL1A1和COL1A2直接相关的基因,实时PCR分析18αGL干预后相关基因表达情况。结果 18αGL能够改善纤维化大鼠I型胶原相关COL1A1和COL1A2的mRNA水平,并且能减少I型胶原的分布。Signal-Net网络分析发现与COL1A1和COL1A2直接相关的基因中,与TGF-β/Smad、Rho/rock、MAPK、PDGF和MMP等信号通路相关,动物体内18αGL可引起RAC、RHOA、HSPB、SMAD3、SP-1和MMP2、MMP9转录水平的下调。结论 18αGL能够显著减少纤维化大鼠肝脏I型胶原的表达,并且从多通路抑制I型胶原COL1A1和COL1A2表达,从而可以多层次,多靶点的改善胶原和影响肝纤维化进程。     

XⅧ型胶原mRNA在实验性肝纤维化大鼠肝脏中的表达

目的 了解ＸⅧ型胶原（ｃｏｌｌａｇｅｎ ＸⅧ，ＣＸⅧ）ｍＲＮＡ在实验性肝纤维化中的定量改变。方法 以逆行胆管硬化注射加结扎的方法制备大鼠胆管堵塞性肝纤维化模型，以假手术组大鼠为对照组。提取肝脏总ＲＮＡ，以核酸酶保护分析（ＲＮＡ酶保护分析）定量测定前胶原α１（ＸⅧ）ｍＲＮＡ水平，并与α（１）和金属蛋白酶组织抑制因子１（ＴＭＰ－１）的ｍＲＮＡ变化相比较。结果 与假手术组大鼠相比，胆管堵塞性肝纤维化大鼠     

骨碎补总黄酮对去卵巢大鼠组织蛋白酶K的影响

目的观察骨碎补总黄酮对去卵巢大鼠骨质疏松模型组织蛋白酶K(Cathepsin K)的血清浓度和左胫骨干骺端基因表达的影响,探讨骨碎补总黄酮防治骨质疏松的机制。方法选取3月龄雌性SD大鼠72只,随机分为6组:高剂量骨碎补总黄酮组[治疗组1,12只大鼠,切除双侧卵巢,给药剂量0.216 g/(kg·d)];中剂量骨碎补总黄酮组[治疗组2,12只大鼠,切除双侧卵巢,给药剂量0.108 g/(kg·d)];低剂量骨碎补总黄酮组[治疗组3,12只大鼠,给药剂量0.054 g/(kg·d)];雌激素组(12只大鼠,切除双侧卵巢,给予结合雌激素片0.1 mg/kg);假手术组(12只大鼠,仅切除腹腔少量脂肪和软组织,以5 mL蒸馏水灌胃);正常组(12只大鼠,不做特殊处理,以5 mL蒸馏水灌胃)。各组均在去卵巢造模成功后开始灌胃,并于造模成功后即刻、3个月、6个月每组处死4只大鼠,无菌条件下抽取静脉血,检测血清Cathepsin K浓度。取左胫骨近端干骺端标本,荧光定量PCR测定Cathepsin K mRNA表达量,用SPSS13.0软件进行数据分析。结果各治疗组、正常组与雌激素组大鼠血清Cathepsin K浓度间差异均有统计学意义(P0.05)。各治疗组与雌激素组左胫骨干骺端Cathepsin K mRNA表达量相比有统计学意义(P0.05)。各治疗组、假手术组与正常组左胫骨干骺端Cathepsin K mRNA表达量相比均有统计学意义(P0.01)。结论骨碎补总黄酮抑制去卵巢大鼠血清Cathepsin K浓度、降低左胫骨干骺端Cathepsin K mRNA表达量的作用,可能是其治疗骨质疏松症的机制之一。     

Estradiol replacement enhances working memory in middle-aged rats when initiated immediately after ovariectomy but not after a long-term period of ovarian hormone deprivation

The goal of the present study was to explore the effects of long-term hormone deprivation on the ability of subsequent estrogen replacement to affect cognition. Female rats, 12 months of age, underwent ovariectomies (n = 30) or sham surgeries (n = 10). Intact rats and 20 ovariectomized rats received cholesterol implants. Ten ovariectomized rats received implants containing 25% estradiol. Five months later, implants were replaced. Half of the ovariectomized rats with cholesterol implants received estradiol implants and half received new cholesterol implants. Rats with estradiol implants received new estradiol implants. Intact rats were ovariectomized and given estradiol implants. Beginning 1 wk later, working memory performance was assessed in an eight-arm radial maze across 24 d of acquisition and during eight additional trials in which a 2.5-h delay was imposed between the fourth and fifth arm choices. Estradiol replacement initiated immediately after ovariectomy at either 12 or 17 months of age significantly improved performance during acquisition and delay trials, compared with control treatment. When estradiol replacement was initiated at 17 months of age, 5 months after ovariectomy, no enhancements were evident. Uteri of rats that experienced delayed estradiol replacement weighed significantly more than uteri of ovariectomized controls but significantly less than uteri of rats that received immediate estradiol replacement. Uterine weight negatively correlated with mean errors during acquisition. These results indicate that whereas chronic estradiol replacement regimens positively affect working memory in middle-aged animals when initiated immediately after ovariectomy, estradiol replacement is not effective when initiated after long-term hormone deprivation.     

补肾活血方对去势大鼠骨质疏松的影响

目的观察补肾活血方对去势大鼠的血生化、骨密度、生物力学及病理学的影响,评价补肾活血方防治去势大鼠骨质疏松的疗效。方法取36只雌性大鼠随机分为对照组、假手术组和补肾活血组。补肾活血组与对照组大鼠行卵巢切除术,假手术组行假手术处理,均饲养3个月后行病理检查确认造模成功。造模成功后各组大鼠分别给予0．9％氯化钠注射液、0．9％氯化钠注射液、补肾活血中药灌胃,3个月后处死取血分离得到血清,分别检测血清雌激素（E：）、碱性磷酸酶（ALP）和骨钙素（BGP）。取大鼠腰椎、股骨测量腰椎的骨密度（BMD）和最大承载力、行股骨病理学观察。结果与对照组比较,补肾活血方组大鼠血清E：升高,差异有统计学意义（P〈0．01）;骨形成指标ALP、BGP上升,差异有统计学意义（P〈0．05）。与对照组比较,补肾活血组大鼠腰椎BMD及最大承载力均升高,差异有统计学意义（P〈0．05）。HE染色病理组织形态观察发现补肾活血方组大鼠骨小梁稍细,无明显变薄,排列尚整齐并连接成网,密度、面积尚正常,部分区域骨小梁间隙略增大,较对照组有明显改善。结论补肾活血方能够提高去势大鼠雌激素水平,促进骨形成,增加骨量,提高骨组织的力学性能,改善骨组织状况,达到防治骨质疏松的疗效。     

生理性雌激素对骨髓源性内皮祖细胞迁移功能的影响

目的研究生理性雌激素对骨髓源性内皮祖细胞（BM—EPCs）迁移功能的影响及其机制。方法雌性BALB／C小鼠随机分成卵巢切除组、假手术组和正常组。ELISA法检测各组血清雌激素浓度。取胫骨和股骨骨髓,培养、鉴定BM—EPCs。Transwell小室检测各组BM．EPCs经或未经CXCR4抑制剂AMD3100处理后向基质细胞衍生因子-1α（SDF-1α）的迁移功能。RT—PCR和流式细胞术检测各组BM-EPCsCXCR4的表达。结果卵巢切除组血清雌激素浓度明显低于假手术组和正常组（P〈0．01）。卵巢切除组BM—EPCs向SDF-1α迁移的数量明显低于假手术组和正常组（P〈0．01）。AMD3100明显抑制BM—EPCs向SDF-1α的迁移功能。卵巢切除组BM—EPCsCXCR4的表达明显低于假手术组和正常组（P〈0．01）。结论生理性雌激素通过调节BM—EPCsCXCR4的表达而增强其迁移功能。     

去卵巢大鼠血清乳铁蛋白与骨密度的相关性研究

目的 探讨去卵巢大鼠血清乳铁蛋白(LF)水平与骨密度(BMD)的关系,为临床应用乳铁蛋白提供实验依据.方法 采用4月龄Wistar雌性大鼠,随机分为假手术组(sham,20只)与去卵巢模型组(ovariectomy,OVX,40只,分为OVX I组与OVX Ⅱ组,各20只),分别于术后14与18周处死OVX I组与OV...     

Further evidence on the role of the hypothalamic afferents on the estrogen-induced prolactin release.

Serum prolactin (Prl) concentrations in ovariectomized rats were low without significant differences between morning and afternoon values. These levels were not affected by either frontal or caudal hypothalamic deafferentation. However, they increased after lesioning the hypothalamic median eminence (ME). Three days after the injection of 20 microgram estradiol benzoate (EB) into ovariectomized non-lesioned rats, a rise in serum Prl occurred in the afternoon but not in the morning. In animals with ME lesions estrogen enhanced both morning and afternoon values. The animals with caudal hypothalamic deafferentation and those which had undergone sham operation showed the same pattern as the normal animals. On the contrary, after estrogen treatment of rats with frontal hypothalamic deafferentation high serum Prl concentration during the morning and low levels in the afternoon were observed. It is concluded that estrogen effects on Prl secretion are in part mediated by frontal neural afferents to the hypothalamus. They would facilitate Prl inhibiting factor (PIF) secretion in the morning and inhibit PIF secretion in the afternoon.     

Immunoreactive dynorphin is regulated by estrogen in the rat anterior pituitary

The pituitary and hypothalamic content of dynorphin was determined by radioimmunoassay and characterized by high-performance liquid chromatography (HPLC) in adult female Sprague-Dawley rats, intact and ovariectomized with and without estrogen treatment. Animals were given estradiol benzoate, or vehicle (oil) by six daily intramuscular injections. Anterior pituitary content of immunoreactive (ir)-dynorphin in ovariectomized rats was approximately twice that of intact animals, and consisted of a single HPLC peak co-eluting with dynorphin 32. Administration of estradiol benzoate (0.06-6 micrograms/day) caused a marked decrease of ir-dynorphin in the anterior lobe of castrate female rats, with a half-maximal effect at 0.2 microgram/day; levels were restored to those seen in intact animals with 6 micrograms estradiol benzoate per day, an effect which was not influenced by concomitant administration of progesterone (1 mg/day), or bromocriptine (100 micrograms/day). In the hypothalamus and neuro-intermediate lobe multiple peaks of immunoreactive dynorphin were seen, coeluting with dynorphin A 1-8, dynorphin A 1-17 and dynorphin 32. Neither castration nor estrogen treatment altered ir-dynorphin content in these tissues. These findings suggest that the ovary exerts a specific modulating influence on AP ir-dynorphin in the rat, and that in addition this inhibition appears to be mediated by ovarian estrogen.     

Aging reduces the efficacy of estrogen substitution to attenuate cardiac hypertrophy in female spontaneously hypertensive rats

Clinical trials failed to show a beneficial effect of postmenopausal hormone replacement therapy, whereas experimental studies in young animals reported a protective function of estrogen replacement in cardiovascular disease. Because these diverging results could in part be explained by aging effects, we compared the efficacy of estrogen substitution to modulate cardiac hypertrophy and cardiac gene expression among young (age 3 months) and senescent (age 24 months) spontaneously hypertensive rats (SHRs), which were sham operated or ovariectomized and injected with placebo or identical doses of 17beta-estradiol (E2; 2 microg/kg body weight per day) for 6 weeks (n=10/group). Blood pressure was comparable among sham-operated senescent and young SHRs and not altered by ovariectomy or E2 treatment among young or among senescent rats. Estrogen substitution inhibited uterus atrophy and gain of body weight in young and senescent ovariectomized SHRs, but cardiac hypertrophy was attenuated only in young rats. Cardiac estrogen receptor-alpha expression was lower in intact and in ovariectomized senescent compared with young SHRs and increased with estradiol substitution in aged rats. Plasma estradiol and estrone levels were lower not only in sham-operated but surprisingly also in E2-substituted senescent SHRs and associated with a reduction of hepatic 17beta-hydroxysteroid dehydrogenase type 1 enzyme activity, which converts weak (ie, estrone) into potent estrogens, such as E2. Aging attenuates the antihypertrophic effect of estradiol in female SHRs and is associated with profound alterations in cardiac estrogen receptor-alpha expression and estradiol metabolism. These observations contribute to explain the lower efficiency of estrogen substitution in senescent SHRs.     

清肝活血方对酒精性肝病大鼠肝组织Ⅰ型胶原表达的影响

目的 :观察清肝活血方对酒精性肝病大鼠肝组织 型胶原表达的影响。方法 :4 5只大鼠用乙醇、玉米油、吡唑等制备酒精性肝病大鼠模型 ,随机均分为模型组 ,清肝活血方低、高剂量组 ,小柴胡冲剂组 ,用免疫组化观察肝组织 型胶原的分布 ,RT- PCR法检测大鼠肝组织 型胶原 m RNA表达 ,并与对照组比较。结果 :酒精性肝病大鼠模型表现为肝功能异常 ,以门冬氨酸氨基转移酶 (AST)变化为显著 ,模型组大鼠肝组织在汇管区有少量 型胶原的分布 ,部分向小叶内延伸 ;正常组大鼠几乎无 型胶原 m RNA表达 ,模型组有明显表达 ,清肝活血方高剂量组 型胶原及其 m RNAR的表达均明显下降 (P <0 .0 5 )。结论 :清肝活血方能有效预防酒精引起的肝损伤、肝纤维化的发生、发展 ,其机制可能与其抑制 型胶原 m RNA表达有关