In Vivo Effects of Ovarian Steroid Hormones on the Expressions of Estrogen Receptors and the Composition of Extracellular Matrix in the Anterior Cruciate Ligament in Rats

Female athletes have a significantly higher rate of anterior cruciate ligament (ACL) injury than their male counterparts. Sex steroid hormones are considered to have an influence as risk factors for female ACL injuries. We hypothesized that estrogen and progesterone have specific and synergistic influences on the composition of extracellular matrix in ACL. By ovariectomy (OVX) followed by subcutaneous estradiol (E2) and/or progesterone (P4) replacement, 40 female rats were divided into 5 groups: E2, P4, combined E2 and P4 (EP), OVX control, and sham group. After 30 days, using undecalcified sections of knee joints in conjunction with immunofluorescence staining of estrogen receptor α and β (ERα and ERβ), collagen types 1 and 3, and cartilage oligomeric matrix protein (COMP), the immunoreactivities of these proteins in two distinct parts of ACL, proximal and middle portions, were compared semiquantitatively among experimental groups. By E2 replacement, the expressions of ERα in ACL fibroblasts were elevated compared to the OVX group. At the proximal portion, the immunoreactivities of type 1 collagen by E2 replacement, type 3 collagen by P4 replacement, and COMP by E2 or P4 replacement were significantly reduced. At the middle portion, the immunoreactivity of type 3 collagen was significantly elevated by E2 replacement. However, no differences were observed between the sham and OVX groups. These findings suggest that ACL is ER-dependent and that ovarian hormones alter ligament tissue composition, especially at the proximal portion. Female hormonal influences are partly involved in the biological properties of ACL.     

去卵巢和雌激素替代治疗对心肌细胞基因表达谱的影响

目的：本实验通过高通量的cDNA微阵列技术，研究去卵巢和雌激素替代治疗对心肌细胞基因表达谱的影响，寻找雌激素的靶基因。方法:用 1 400 个基因构建的cDNA微阵列检测假手术组（Ⅰ）、去卵巢组（Ⅱ，去势组）和雌激素替代治疗组（Ⅲ，替代组）3组SD雌鼠心肌组织的基因表达差异,随机选2个基因用半定量RT-PCR验证检测结果。结果:假手术组和去势组共检出心肌差异表达的基因177个，其中去卵巢导致上调的基因91个，下调的基因86个；去势组和替代组共检出心肌差异表达的基因164个，其中雌激素替代治疗后导致上调的基因113个，下调的基因54个。Ⅰ/Ⅱ和Ⅲ/Ⅱ比较，相同的差异表达基因54个，雌激素明显影响心肌膜通道和载体（18个）、细胞受体（9个）、信号转导相关基因（7个）和细胞代谢（6个）的mRNA水平。而大部分基因（45个）是在去势组表达下调，在雌激素替代组表达上调。RT-PCR实验证实了cDNA微阵列结果 。结论：长期雌激素替代治疗明显影响心肌细胞膜通道和载体、信号转导、细胞受体和细胞代谢等相关基因的表达。长期雌激素替代治疗可通过增加Na+,K+-ATPase和Na+/H+交换蛋白的基因表达，稳定心肌细胞内Na+和K+的浓度。雌激素还可抑制多巴胺受体基因的表达，预防心肌肥大、充血性心衰等心脏疾病的发生。     

The pattern of distribution of PGP 9.5 and TNF-alpha immunoreactive sensory nerve fibers in the labrum and synovium of the human hip joint

To date, there has been no report clarifying the existence of sensory nerve fibers as the origin of the hip joint pain of osteoarthritis. We examined the existence of sensory nerve fibers in osteoarthritis (OA), osteonecrosis of the femoral head (ONFH), and femoral neck fracture of the human hip joint. Ten labra of 10 human hip joints were harvested during a total hip arthroplasty. Each labrum was separated into 12 sections and we used three sections for analysis, which included 2 weight-bearing and 1 non-weight-bearing portion. Protein gene product 9.5 (PGP 9.5) immunoreactive sensory nerve fibers were found in the labrum and synovium harvested from the weight-bearing portion in the OA group. Some of these sensory nerve fibers were also positive for tumour necrosis factor alpha (TNF). The PGP 9.5 immunoreactive sensory nerve fibers existed in the labrum tissue and inflammatory TNF positive cells were observed in the hyperplastic synovium. On the other hand, we could not demonstrate PGP 9.5 or TNF immunoreactive sensory nerve fibers and cells in any of the ONFH group or the non-weight-bearing portion in the OA group. These data suggest that the pain of ONFH and OA of the hip joint have different pathogenetic mechanisms and that the invasion of sensory nerve fibers containing TNF may be involved in the pathogenesis of pain in the human hip joint affected by OA.     

雌激素对SAMP8小鼠学习记忆及海马CA1区神经元的影响

目的 观察雌激素对SAMP8鼠学习记忆及海马神经元的影响. 方法 将6月龄SAMP8鼠45只分为假手术组(sham组)、去卵巢组(OVX组)和去卵巢+雌激素组(OVX+E组)3组,并用同龄正常老化SAMR1小鼠作为同源对照组.采用Morris水迷宫实验检测小鼠学习记忆能力,苏木素-伊红染色和免疫组织化学显示海马CA1区神经元及神经型一氧化氮合酶(nNOS)阳性神经元的变化,流式细胞术检测其nNOS的表达量. 结果 OVX组与sham组相比,逃避潜伏期明显延长(P<0.05),跨越平台次数显著减少(P<0.05).雌激素补充治疗能改善学习记忆能力,与sham组比较差异无统计学意义(P>0.05);OVX组海马CA1区神经元病变严重,且CA1区nNOS阳性神经元的数量、吸光度和海马nNOS荧光指数(FI)值均低于sham组(P<0.05);给予雌激素后,OVX+E组各项实验结果与OVX组相比差异有统计学意义(P<0.05),与sham组相比,差异无统计学意义(P>0.05). 结论 雌激素能够改善小鼠的学习记忆能力,有效保护海马CA1区的神经元,提高海马CA1区nNOS阳性神经元的表达.     

雌激素改善卵巢切除合并慢性铝中毒对大鼠心脏Cx43表达和金属元素变化的影响

目的 探讨雌激素治疗卵巢切除合并慢性铝中毒大鼠,对心脏间隙连接蛋白43(Cx43)表达和金属离子含量的影响. 方法 40只6月龄雌性SD大鼠,随机分为卵巢假切除组(Sham组),卵巢切除组(OVX组)、卵巢切除合并慢性铝中毒组(OVX+Al组)和卵巢切除合并慢性铝中毒及尼尔雌醇灌胃组(OVX+Al+E2组).于术后3个月,利用离子体发射光谱仪测定心脏金属元素含量,采用免疫组织化学和图像分析法观测心肌细胞Cx43表达.结果 1. Cx43表达:Sham组心房肌Cx43遍布于心肌细胞侧面连接和端闰盘处.心室肌分布于心肌闰盘处.OVX组心房肌的Cx43颗粒部分由细胞侧-侧连接处移至闰盘处或杂乱排列,心室肌Cx43由闰盘处移至细胞侧-侧连接处或杂乱地无序排列,少部分出现在细胞质中,OVX+Al组Cx43排列类似于OVX组,且更加紊乱.OVX+Al+E2组心房肌Cx43回复正常分布,但心室肌未发现回复.2.图像分析结果,各组大鼠心肌细胞Cx43的面积构成比比较无显著差异.3.金属元素含量:在Sham组,金属元素在心脏含量的排列顺序如下:Mg＞Ca＞Fe＞Zn＞Al＞Si＞Cu＞Mn＞Se和Cd.各组间比较具有显著差异的是:与Sham组比较,OVX组Zn降低;OVX+Al+E2组Al、Cd、Si、Se均升高;OVX+Al组与OVX组比较,Si升高、Zn降低.OVX+Al+E2组与OVX+Al组比较, Cd、Mn、Se升高. 结论雌激素改善卵巢切除及加铝后引起的心脏金属元素含量改变和心肌细胞间隙连接蛋白Cx43重构.     

17β-雌二醇对去势大鼠子宫内膜厚度的影响

目的:探索外源性使用雌激素对去势后大鼠子宫内膜厚度的影响。方法:96只雌性成年SD大鼠,随机分为假手术组、模型组和17β-雌二醇(17β-estradiol,E2)治疗组,模型组和E2治疗组行去势手术,并且E2组给予不同剂量、不同时间的E2背部皮下注射后处死,假手术组于动情前期处死,取子宫标本,行HE染色,在200倍显微镜下随机选取六个位置拍照,测量子宫腔上皮厚度。结果:去势E2治疗组大鼠子宫的发育与替代雌激素的用量呈明显的量效关系及时效关系。E2浓度在6μg.只-1,连续使用2 d时,去势大鼠子宫内膜形态学检查与假手术组组基本相似,子宫腔上皮厚度比假手术组大鼠增加8%,可认为是合理的雌激素替代剂量与时间。     

Estrogen replacement reverses ovariectomy-induced vaginal hyperalgesia in the rat

OBJECTIVES: The loss of ovarian function in women through aging or oophorectomy is often associated with the development of vaginal hyperalgesia that can be alleviated with estrogen replacement. This study examined if ovariectomy in rats would similarly give rise to vaginal hyperalgesia, and, if so, whether estrogen replacement would alleviate it. METHODS: Female rats were trained to perform an operant response to escape vaginal distention delivered by inflating a balloon located in mid-vaginal canal. Percent escape responses to eight different volumes of distention measured in normally cycling rats were compared with measures made in the same rats following ovariectomy (OVX) or sham ovariectomy (shamOVX), and then, in the OVX group, estrogen replacement (OVX+E2). Pressures exerted by the eight volumes on the vaginal wall were also measured, thereby permitting assessment of vaginal tone. RESULTS: Whereas overall escape response percentages after OVX, but not shamOVX, were significantly higher to the largest six distention volumes compared with responses during cycling, there were individual differences in the amount of hyperalgesia. Following OVX+E2, escape response percentages decreased in all but one rat. Vaginal tone after OVX, shamOVX or OVX+E2 did not differ from overall vaginal tone in cycling rats. CONCLUSIONS: Ovariectomy in rats evokes a variable amount of vaginal hyperalgesia that can be alleviated by estrogen replacement in most cases. Thus, the ovariectomized rat appears to provide a useful model for the study of mechanisms underlying the dyspareunia that is associated with loss of ovarian function in women.     

雌激素替代治疗对中年卵巢切除大鼠大脑白质、海马内髓鞘及Lingo-1蛋白的影响

目的检测经短期雌激素替代治疗(ERT)后中年卵巢切除大鼠大脑白质及海马内髓鞘相关指标及Lingo-1的表达,探讨雌激素对髓鞘作用的可能机制。方法 24只中年雌性SD大鼠行双侧卵巢切除术(OVX)后,随机分为安慰剂治疗组(OVX+Veh组)和雌激素替代治疗组(OVX+E组)。ERT 1个月后,Morris水迷宫检测大鼠空间学习和记忆能力;从各组大鼠随机选取10只,透射电子显微镜观察大脑白质及海马内髓鞘的超微结构;Western blot检测大脑白质及海马内髓磷脂碱性蛋白(MBP)及Lingo-1的含量;免疫组化方法检测Lingo-1在大脑白质及海马的分布。结果 OVX+E组大鼠在定位航行实验中的潜伏期显著短于OVX+Veh组大鼠(P0.05);OVX+Veh组大鼠大脑白质和海马存在显著的髓鞘结构变性;OVX+E组大鼠大脑白质和海马中MBP的含量均显著高于OVX+Veh组(P0.05),而OVX+E组大鼠大脑白质和海马中Lingo-1的含量及分布均显著低于OVX+Veh组(P0.05)。结论1个月的ERT对中年卵巢切除大鼠的认知功能及大脑白质和海马内的髓鞘具有明显的保护作用,这种保护作用可能与雌激素下调大脑白质和海马内Lingo-1蛋白的表达有关。     

Effects of ovariectomy and estrogen on skeletal muscle function in growing rats

This study examined the effect of estrogen replacement on soleus muscle size and contractile function in ovariectomized rats during physiological growth. Seven week old female Sprague-Dawley rats were assigned to one of three treatment groups: (1) control animals (SHAM), (2) ovariectomized animals without estrogen replacement (OVX/CO), and (3) ovariectomized animals with 17 beta-estradiol replacement (OVX/E2). OVX/CO and OVX/E2 animals were pair-fed to SHAM animals to rule out the potentially confounding effect of differences in food intake. Rats were sacrificed 4 weeks after surgery and the soleus muscle was removed for analysis. Estrogen replacement reduced body weight, relative body weight gain, and soleus muscle fiber size despite all groups having a similar food intake. Ovariectomy alone had no effect on any of these parameters suggesting that estrogen may inhibit skeletal muscle growth when it is the only ovarian hormone present. Neither ovariectomy nor estrogen replacement affected maximal specific isometric force. Estrogen replacement increased half relaxation time. Ovariectomy resulted in a reduction in time to peak tension that was reversed with estrogen replacement. This reduction was not accompanied by a change in myosin heavy chain composition implying that calcium handling may have been altered. Results from this study suggest that estrogen affects skeletal muscle growth and twitch kinetics.     

Neurovascular plasticity in the knee joint of an arthritic mouse model

Lower numbers of neuropeptide-containing fibers in arthritic joints have been found as compared to control joints. This may be the result of fiber depletion, necrosis of fibers, or proliferation of soft tissues without neural sprouting. To discriminate between these possibilities, we studied the relationships between soft tissue proliferation, changes in vascularity of synovial tissues, and changes in joint innervation during arthritis. Arthritis was induced in the knee joint of mice by a single subpatellar injection of methylated bovine serum albumin after previous immunization. Antibodies to protein gene product 9.5, S-100, and growth-associated protein-43 (GAP-43) were used to study the general innervation pattern. Antibodies to calcitonin gene-related peptide (CGRP), vasointestinal polypeptide (VIP), substance P (SP), and tyrosine hydroxylase (TH) were used to localize sensory (SP, CGRP, VIP) and sympathetic (TH) fibers. Blood vessels of the joint were studied with ink perfusion, GAP-43, and a vascular marker (LF1). Directly after the induction of arthritis, the synovial cavity was enlarged and filled with leukocytes. From day 4 onward, small sprouting blood vessels penetrated the avascular mass of cells in the joint cavity. After 1 week, the vascular sprouting activity and GAP-43 immunoreactivity were maximal, and after 2 weeks, vascular sprouting activity diminished. In the subsequent period, the synovia slowly regained their prearthritic appearance and thickness. The most pronounced changes in the general staining pattern of CGRP, SP, VIP, and TH were found in the periosteum. From 2 days to 4 weeks after the induction of arthritis, the layer of SP, CGRP, and VIP fibers in the femoral periosteum was thicker and more irregular. GAP-43 staining showed many terminal varicosities, which suggested sprouting of nerve fibers. From 2 days to 2 weeks after the induction of arthritis, the SP and CGRP fibers in the periosteum showed gradual depletion. In the thickened subsynovial tissues that were revascularized, no ingrowth of neural elements was found. As the total number of nerve fibers in the synovial tissue did not change, large parts of the synovia directly facing the joint cavity were not innervated at 1 week after the induction of arthritis. These results strongly suggest that periosteal SP and CGRP fibers were depleted during arthritis. Synovial proliferation without concomitant fiber growth is the main cause of the reduced number of immunocytochemically detectable fibers in the mouse arthritic knee joint.     

17beta-estradiol attenuates hippocampal neuronal loss and cognitive dysfunction induced by chronic restraint stress in ovariectomized rats

Several lines of evidence suggest that hormonal changes after menopause may play an important role in the incidence of cognitive dysfunction, and also in the development of Alzheimer's disease. In this study, we investigated the effect of estrogen on cognitive function in rats under different stress environment. Female rats were divided into four groups: two groups were ovariectomized (OVX) and two were sham-operated. One group each of OVX and sham rats was kept in a normal environment, and the other groups were assigned to a daily restraint stress (6 h/day) for 21 days from 2 months after the operation. Following the stress period, subjects were tested for performance in novel object recognition test and then used for morphological and neurochemical analyses. The OVX plus stress (OVX/stress) group showed a significant impairment of recognition of novel objects, compared with the other groups. The OVX/stress group also showed a marked decrease in the number of pyramidal cells of the CA3 region and levels of brain-derived neurotrophic factor mRNA in the hippocampus. We further examined the effect of estrogen against cognitive dysfunction and hippocampal changes of OVX/stress rats. Vehicle or 17beta-estradiol (E2) at 20 microg/day was s.c. administered to OVX/stress rats from 2 days before the stress period to the end of behavioral analysis through an implantable osmotic pump. Chronic E2 treatment decreased stress response and improved the cognitive and morphological impairments relative to vehicle group. These data have important implications for cognition enhancing effect of estrogen treatment in postmenopausal women.     

Distribution and origin of nerve fibers in the rat temporomandibular joint capsule

 The distribution and origin of nerve fibers containing neuropeptides and NOS projecting to the temporomandibular joint capsule (TMJ) of the rat were studied by retrograde tracing in combination with immunocytochemistry. Numerous nerve fibers were seen in the TMJ as revealed by the neuronal marker protein gene product 9.5. Nerve fibers containing neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating peptide (PACAP), substance P (SP), calcitonin gene-related peptide (CGRP), and nitric oxide synthase (NOS) were seen in the synovial membrane, the joint capsule and entering the articular disc. Injection of the retrograde tracer True Blue (TB) into the TMJ resulted in the appearance of numerous labeled nerve cell bodies in the trigeminal and superior cervical ganglia, and moderate numbers in the nodose, the otic, the sphenopalatine, the stellate and the dorsal root ganglia at levels C2–C5. Most of the TB-labeled cell bodies in the superior cervical and stellate ganglia contained NPY. In the trigeminal ganglion, numerous TB labeled cell bodies contained CGRP and a minor population stored SP, a few cell bodies were seen to store NOS or PACAP. In the sphenopalatine and otic ganglia, TB labeled cell bodies contained NOS or VIP. In the nodose ganglion, labeled cell bodies contained CGRP; other labeled cell bodies harbored NOS. In the cervical dorsal root ganglia, the majority of the labeled cell bodies stored CGRP and smaller populations stored SP and PACAP. Thus, the innervation of the TMJ is complex and many different ganglia are involved. Accepted: 13 October 1997     

Distribution of CGRP, substance P, VIP and somatostatin immunoreactive nerve fibers in the internal gills of larvae of the bullfrog, Rana catesbeiana.

CGRP, substance P (SP), VIP and somatostatin were demonstrated in the internal gills of larval bullfrogs using the immunohistochemical peroxidase-antiperoxidase method. Three groups of immunoreactive fibers were distinguished by their distribution area. The first group includes CGRP, SP and VIP immunoreactive fibers running in the connective tissue of the gill tufts. These fibers were associated with the capillaries. Some CGRP fibers were distributed similarly to SP fibers, and the density of VIP immunoreactive fibers was low. The second group includes CGRP, SP, VIP and somatostatin fibers distributed in the connective tissue surrounding the ceratobranchialia. The third group includes CGRP, SP and somatostatin fibers located in the branchial muscle. Their terminals appeared to be neuromuscular junctions. No immunoreactivity of leu- or met-enkephalins was found in the internal gills. From these findings, the first group of fibers is presumed to be involved in modulating ion transport of the internal gills. The second group of fibers except for the somatostatin fibers is thought to be continuations of the first group of fibers. The third group of fibers may possibly be involved in the modulation of transmissions at the neuromuscular junction. It is unclear whether somatostatin terminals are also involved in this.     

Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats

Drospirenone (DRSP) is a progestin with anti-aldosterone properties and it reduces blood pressure in hypertensive women. However, the effects of DRSP on endothelium-dependent coronary vasodilation have not been evaluated. This study investigated the effects of combined therapy with estrogen (E2) and DRSP on endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX) spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87) at 12 weeks of age were randomly divided into sham operated (Sham), OVX, OVX treated with E2 (E2), and OVX treated with E2 and DRSP (E2+DRSP) groups. Hemodynamic parameters were directly evaluated by catheter insertion into the femoral artery. Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial bed was assessed using isolated hearts according to a modified Langendorff method. Coronary protein expression of endothelial nitric oxide synthase and estrogen receptor alpha (ER-α) was assessed by Western blotting. Histological slices of coronary arteries were stained with hematoxylin and eosin, and morphometric parameters were analyzed. Oxidative stress was assessed in situ by dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial dysfunction, which was prevented by both treatments. However, the vasodilator response in the E2+DRSP group was significantly higher at the three highest concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was restored by both treatments. Morphometric parameters and oxidative stress were augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2 and DRSP may be an important therapeutic option in the prevention of coronary heart disease in hypertensive post-menopausal women.     

雌激素对抑郁症小鼠行为学和脑组织单胺类递质的作用

目的:探讨雌激素低下对抑郁症模型小鼠行为学影响及神经生化机制。方法:清洁级昆明小鼠随机分为假手术组(Sham)、卵巢切除组(OVX)、慢性应激组(CUMS)、卵巢切除+慢性应激组(OVX+CUMS)和雌激素治疗组(E组,0.15 mg/kg),每组10只。给药组于每日应激前1 h,ig给药,其余各组给予等体积生理盐水,共计21 d。采用卵巢切除法(OVX)制备雌激素低下动物模型,采用CUMS法制备抑郁症小鼠模型。观察各组小鼠一般体征,行阴道上皮角化实验,通过旷场实验(OFT)、强迫游泳实验(FST)及体重测试(BWM)观察其行为学变化,采用ELISA法检测脑组织单胺类递质五羟色胺(5-HT)及多巴胺(DA)含量变化。结果:OVX小鼠,阴道细胞涂片未见动情周期变化连续7 d。模型小鼠在第21 d,与Sham组比较,(1)OVX和CUMS小鼠体重增加(P﹤0.01),而OVX+CUMS则体重下降(P﹤0.01);(2)在OVX和CUMS小鼠,OFT水平和垂直运动得分减少(P﹤0.01),而在E组小鼠,OFT水平和垂直运动得分增加(P﹤0.05);(3)在OVX和CUMS小鼠,FST不动时间减少(P﹤0.01),但在E组小鼠,FST不动时间增加(P﹤0.01)。(4)在OVX组小鼠,阴道脱落细胞呈现大量白细胞和少量上皮细胞。在CUMS和OVX小鼠,脑组织5-HT和DA含量减少(P﹤0.01),但在E组小鼠,脑组织中5-HT、DA含量增加(P﹤0.05,P﹤0.01)。结论:小鼠抑郁行为可以由于雌激素低下诱发,并且与脑组织5-HT和DA含量下调有关。补充雌激素可能通过增加单胺类递质5-HT和DA含量在脑组织,从而改善小鼠抑郁行为。     

内皮源性硫化氢在雌激素抗动脉粥样硬化中的作用及机制

 目的：探讨内皮源性硫化氢（H2S）在雌激素诱导的抗动脉粥样硬化过程中的作用及其机制。方法：在体外培养的人脐静脉内皮细胞（HUVECs）上观察17β-雌二醇（E2）促进H2S快速释放的效应,并进一步观察雌激素受体在此过程中的作用。在去势雌性ApoE–/–C57BL/6小鼠中建立动脉粥样硬化模型,实验分为去势组（OVX）、去势+E2治疗组（OVX+E2）、去势+E2+内源性H2S生成酶抑制剂DL-炔丙基甘氨酸(PPG)治疗组（OVX+E2+PPG）,观察各组大鼠血液中H2S的浓度和动脉粥样斑块大小。结果：E2可以促进HUVECs快速释放H2S,且具有时间效应和浓度效应。雌激素受体α亚型激动剂丙基吡唑三醇(而不是β亚型激动剂二芳丙腈）可以模拟E2促H2S释放效应,雌激素受体拮抗剂ICI 182780可以阻断E2促H2S释放效应。在动物模型上,与OVX相比,OVX+E2组动脉粥样硬化明显改善,血液中H2S浓度升高;而OVX+E2+PPG组动脉粥样硬化无明显改善,H2S浓度无明显差异。结论: 雌激素通过细胞膜上的ERα促进内皮源性H2S的快速释放,H2S在雌激素抗动脉粥样硬化的过程中起着重要作用。     

In vivo release rates of substance P in the preoptic/anterior hypothalamic area of ovariectomized and ovariectomized estrogen-primed rats: correlation with luteinizing hormone and prolactin levels

Push-pull cannulae were implanted into the preoptic/anterior hypothalamic area (POA) of ovariectomized (OVX) rats. After recovery animals were treated with estradiol (E2) or corn oil and they were perfused 3 days later. Substance P (SP) concentrations were measured in 15 min perfusate fractions, blood samples were taken at similar intervals. SP concentration in POA perfusates were readily measurable. Following estrogen priming SP release increased significantly each afternoon prior to the estrogen induced prolactin and luteinizing hormone (LH) surges. No such increase of SP release was observed in OVX rats with constant LH and prolactin levels throughout the day. Mean SP rates in OVX rats were significantly higher in comparison to OVX estrogen-primed rats. These results indicate that SP may be involved in the feedback mechanisms of estrogen on prolactin and LH release. Authenticity of SP in POA perfusates was made probable by high-performance liquid chromatography (HPLC) where synthetic SP eluted at the same retention time as the signal measured in push-pull perfusates.     

兔膝骨关节炎合并骨质疏松症动物模型的建立

背景：临床发现同时患有骨质疏松症和骨关节炎患者占相当大的比例,而且目前对骨质疏松与骨关节炎相互关系的认识不一致。 目的：建立骨关节炎合并骨质疏松症的动物模型。 方法：将14只新西兰大白兔随机等分为模型组和正常组。模型组新西兰大白兔行双侧卵巢切除,正常组新西兰大白兔不作任何处理。 结果与结论：去除卵巢10周后,模型组大白兔关节软骨出现明显的退变,血清雌二醇、股骨骨密度水平较正常组显著下降(P < 0.01),而关节软骨Mankin评分比正常组显著增高(P < 0.01);且软骨Mankin评分与骨密度和血清雌二醇呈负相关,而骨密度与血清雌二醇水平呈正相关,表明实验成功建立了兔膝骨关节炎合并骨质疏松症动物模型。     

类风湿性关节炎滑膜组织中PTTG1和MMP—2的表达及意义

目的 检测类风湿性关节炎(rheumatoid arthritis,RA)患者滑膜被覆细胞及滑膜下组织中垂体肿瘤转化基因1(pituitary tumor transforming gene 1,PTTG1)及MMP-2的表达及分布状况,探讨其在RA发病中的作用.方法 采用免疫组化SP法检测68例RA患者,14例骨性关节炎(osteoarthritis,OA)患者滑膜被覆细胞及滑膜下组织中PTTG1及MMP-2的表达状况.结果 PTTG1在RA组、OA组阳性率分别为64.7%和21.4%;MMP-2在RA组、OA组阳性率分别为73.5%和28.6%,差异具有统计学意义(P<0.05),且PTTG1和MMP-2之间表达具有相关性(rs=0.776,P<0.05).结论 PTTG1和MMP-2在RA组滑膜组织的表达均明显升高,且二者之间的表达具有相关性,从而证实其在RA的发病机制中可能具有一定的作用.     

发育中的人胎小肠神经肽的研究

目的　研究人胎小肠壁P物质 (SP)和降钙素基因相关肽 (CGRP) IR肽能神经的分布和发育规律。方法　苏木精伊红 (HE)染色和免疫组织化学ABC法。结果　在胎儿发育过程中 ,小肠组织形态及其神经肽的发生、分化出现明显的变化 ,其分化由十二指肠向空肠、回肠依次进行。第 14周开始 ,胎儿小肠壁粘膜下层、肌层间结缔组织中偶见SP能、CGRP能神经纤维及神经元免疫反应产物 ,第 34周至 38周时反应最强 ,神经元从浅棕色到深棕色 ,神经纤维呈串珠状或点线状。从SP、CGRP免疫组织化学相邻切片上看 ,两者部分存在共存现象。结论　人胎小肠壁存在SP IR、CGRP IR肽能神经 ,粘膜下和肌间神经丛存在SP IR、CGRP IR肽能神经元和神经纤维 ,二种神经肽的分布有差异