首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 15 毫秒
1.
Regulation of adrenergic activity in penile corpus cavernosum   总被引:4,自引:0,他引:4  
The regulation of adrenergic activity in the penis was investigated by studying human and rabbit corpus cavernosum strips in organ chambers and measuring the release of norepinephrine from adrenergic nerve terminals. Electrical field stimulation of corporal strips caused frequency-dependent contractions which were potentiated by cocaine and attenuated by the alpha 1 adrenoceptor antagonist prazosin (10(-7) M), but not by the alpha 2 adrenoceptor antagonist rauwolscine (10(-7) M). Norepinephrine caused concentration-dependent contractions of corporal strips, which were attenuated by prazosin and rauwolscine. Acetylcholine and physostigmine attenuated adrenergic nerve mediated contractions and also significantly reduced electrically-induced norepinephrine release. These effects were reversed by atropine. Atropine alone enhanced electrically-induced norepinephrine release. Rauwolscine inconsistently enhanced adrenergic nerve mediated contractions but augmented norepinephrine release caused by electrical stimulation. The alpha 2 adrenoceptor agonist clonidine inhibited electrically-induced norepinephrine release. Vasoactive intestinal polypeptide (VIP) attenuated adrenergically-mediated contractions, but had no effect on electrically-induced release of norepinephrine. It is concluded that: 1) contraction of corporal smooth muscle is mediated by postjunctional alpha 1 adrenoceptors; 2) adrenergic activity is modulated by prejunctional alpha 2 adrenoceptors and cholinergic nerves via prejunctional muscarinic receptors; and 3) the putative nonadrenergic noncholinergic neurotransmitter, VIP, has no apparent role in the regulation of adrenergic nerves.  相似文献   

2.
A rare complication of fracture of the corpus cavernosum following penile venous surgery is described here. Problems of diagnosis and management are briefly outlined.  相似文献   

3.
阴茎海绵体α1-肾上腺素受体亚型的实验研究   总被引:2,自引:0,他引:2  
Peng M  Zhang Y  Xue Z  Han Q 《中华外科杂志》1998,36(8):497-499
目的研究兔阴茎海绵体α1肾上腺素受体(α1AR)三种亚型的分布及其介导的收缩效应。方法采用放射配基结合实验和离体组织收缩功能实验。结果在放射配基结合实验中,标本经氯乙基可乐定(CEC)预处理后,125IBE与α1AR最大结合容量(Bmax)由746±236fmol/mg蛋白下降至214±71fmol/mg蛋白(P<001)。α1AR选择性拮抗剂竞争抑制曲线经两位点分析显示,α1A、α1DAR和α1BAR分别约占20%、25%、55%。在收缩功能实验中,标本经用CEC预处理后,去甲肾上腺素(NE)介导的最大收缩无明显下降,α1AR亚型选择性拮抗剂5MU和BMY7378抑制NE介导阴茎海绵体收缩的拮抗指数(pA2)值与克隆α1AAR亚型的解离常数(KI)值相符合。结论在兔阴茎海绵体中α1AR三种亚型均有分布,但功能性α1AR则以α1AAR为主。  相似文献   

4.
To assess cavernous nerve integrity, we measured evoked cavernous activity (ECA) in 16 men who underwent nerve sparing radical prostatectomy (NS group) and 11 men who underwent non-nerve-sparing surgery (non-NS group). The right median nerve was electrically stimulated and ECA was recorded with two concentric electromyography needles placed into the right and left cavernous bodies. We simultaneously recorded hand and foot sympathetic skin responses (SSRs) as controls. All subjects had recordable SSR, and all subjects following nerve-sparing radical prostatectomy had reproducible ECA. Of the 11 non-NS subjects, eight had no response, indicating interrupted corporal innervation. Three subjects had reproducible ECA, one of whom had a very late latency, suggesting residual innervation was present. The mean latencies of ECA were similar to foot SSR mean latencies (P>0.05), but not to hand SSR latencies. The non-NS group was significantly different from the NS group for the presence of ECA (P<0.001). ECA is a viable method of evaluating the autonomic innervation of the penis.  相似文献   

5.
The objective of this study was to investigate structural changes in the penile corpus cavernosum of prepubertal chronically stressed rats. Eight Wistar rats were assigned into the stress group (SG) and were submitted to 2 hours of tube restraint daily, from the fourth to the ninth week of life. Another 7 rats were used as the control group (CG). All animals were weighed weekly. At day 64, animals were sacrificed by anesthetic overdose, blood was collected for testosterone concentration by radioimmunoassay, and penis and adrenal were collected. Adrenal mass index and testosterone serum levels were used to assess the efficacy of the stress stimulus. The surface density of connective tissue and smooth muscle fibers of corpus cavernosum were measured on Masson trichromic-stained slices. Picrosirius red-stained slices were assessed under polarized light for different types of collagen. The Student's t test was applied for mean comparisons, with P < .05 considered significant. Testosterone serum concentrations decreased and adrenal mass index increased, confirming the effectiveness of the stress protocol. Smooth muscle fibers of corpus cavernosum decreased from 14.07% (CG) to 8.98% (SG) (P = .02), and connective tissue increased from 53.66% (CG) to 64.47% (SG) (P = .01). Also, there was a higher level of type I collagen in the SG animals compared with the CG. Stress stimuli induced structural changes in the corpus cavernosum of rats suggestive of penile fibrosis, which may play a role in erection dysfunction.  相似文献   

6.

OBJECTIVE

To clarify the physiological effects of aldosterone on human penile corpus cavernosum (hPCC) tissue, as aldosterone has a wider physiological action than just the maintenance of electrolyte balance, and there are mineralocorticoid receptors, i.e. aldosterone receptors, in hPCC tissue.

MATERIALS AND METHODS

Specimens of hPCC were obtained from 10 patients (mean age 38 years, range 21–75), with informed consent and approval by the local ethics committee. One patient had a penectomy because of penile cancer, and nine had a penile biopsy because of erectile dysfunction. Patients with diabetes mellitus, hypertension or ischaemic heart disease were excluded. In a pharmacological study we evaluated the effect of aldosterone on the isolated hPCC tissues.

RESULTS

Aldosterone caused no significant change in resting tension and did not affect the nitric oxide‐dependent relaxation reaction. However, the dose–response curve of noradrenaline was shifted to the left when the strip preparation was treated with aldosterone (1 × 10?5m ) for 20 min before administering noradrenaline. Moreover, the shift to the left was completely blocked when spironolactone (anti‐aldosterone agent) was added as a pre‐treatment. Pre‐treatment with aldosterone also significantly extended the mean (sem ) time required to reach 50% relaxation of a noradrenaline‐induced contraction, of 9.3 (1.5) min, vs the control, of 5.2 (1.0) min (P = 0.002).

CONCLUSION

Aldosterone has no direct contractile action or a relaxant action on human penile cavernous tissue, but acts to significantly enhance the noradrenaline‐induced contraction. The effect on the noradrenaline‐induced contraction is probably caused by aldosterone enhancing the affinity of the α‐receptors for noradrenaline in hPCC. We suggest that aldosterone acts to enhance contraction of hPCC tissue, and is one of the restraining factors for human penile erection.  相似文献   

7.
The noradrenaline (NA) concentration in the rat corpus cavernosum (CC) increased to approximately 350% of control values after about 8 weeks of hyperglycaemia induced by the intraperitoneal injection of streptozotocin (STZ) at 10 weeks of age. These changes were maintained for at least a further 32 weeks of hyperglycaemia and occurred without any significant change in the weight in the tissue. Smaller but significant increases in NA concentration occurred in the glans penis (GP) reaching 150-175% of the control levels during the period of prolonged hyperglycaemia. In contrast, there was no significant change in the NA concentration in the penile urethra. Measurements have also been made that relate to changes in the synthesis and reuptake of NA in the CC during the period during which high NA concentration is maintained. Immunohistochemical studies for the synthetic enzyme tyrosine hydroxylase in the CC indicate that the intensity of staining in the tissue had increased after 10, 20 and 32 weeks of hyperglycaemia, relative to the tissues from control animals. Dilated nerve fibres and engorged endings were present in the CC of the diabetic animals at these times. Reuptake of tritiated NA by the terminal axonal membranes in the CC was raised to 181% of control values after 12 weeks of hyperglycaemia (P<0.05), but later declined to values that are not significantly different from the control levels (after 26 and 64 weeks of hyperglycaemia). There are few studies of the effects of prolonged diabetes on functional aspects of sympathetic postganglionic neurones in the CC, and this paper suggests that the changes described represent remodelling of noradrenergic axonal terminals starting about after 8-10 weeks of hyperglycaemia; this delay in onset of the neuropathic changes is also a feature of type I diabetes in humans.  相似文献   

8.
目的 探讨阴茎海绵体中肌源性干细胞(MDSCs)的分离与表型鉴定的方法.方法 取2个月龄SD大鼠阴茎海绵体组织,用0.5%Ⅰ型胶原酶、0.1%胰蛋白酶进行酶消化初步分离.应用改良的Preplate差速贴壁法进一步行细胞纯化,细胞培养1h,贴壁细胞为PP1;未贴壁细胞转瓶培养2h,贴壁细胞为PP2;未贴壁细胞再次转瓶培养18h,贴壁细胞为PP3;此后,每次间隔24h转瓶培养依次获得的贴壁细胞为PP4、PP5、PP6,观察细胞形态变化.流式细胞仪检测PP3、PP6细胞中干细胞抗原l (Sca-l)和结蛋白(Desmin)的阳性表达量;Western blot检测PP1 ~ PP6细胞中Sca-1和Desmin的阳性表达;免疫荧光细胞化学法检测Sca-1、Desmin、Sca-1/Desmin在PP6细胞中的表达.结果 PP1~ PP6细胞贴壁能力逐渐减慢,PP6细胞贴壁最慢,2~3d后才开始贴壁成圆形或短梭形.流式细胞仪检测结果显示,PP3细胞中Sca-1阳性表达量为(0.3±0.2)%,与同型对照组比较差异无统计学意义(P>0.05),Desmin阳性表达量为(15.3±1.5)%,与同型对照组比较差异有统计学意义(P<0.05);PP6细胞中Sca-1、Desmin阳性表达量分别为(5.7±0.7)%、(41.1±1.6)%,与PP3比较差异均有统计学意义(P<0.05).Western blot显示PP1 ~ PP5细胞中未检测到Sca-1蛋白明显表达,但在PP6细胞中则检测到Sca-1蛋白的表达,Desmin蛋白在PP1 ~ PP6细胞中表达逐渐增强.免疫荧光细胞化学显示在PP6细胞中有少量细胞表达Sca-1、散在分布、以胞质表达为主;表达Desmin细胞聚集、数量较多、主要表达于胞质;亦发现有极少量双阳性标记细胞(Sca-1/Desmin),共同表达于同一细胞的胞质.结论 在大鼠阴茎海绵体中分离出既有于细胞表型又有肌源性表型的细胞,提示此类细胞为MDSCs.  相似文献   

9.
Electrical activity of the corpus cavernosum in denervated rats   总被引:2,自引:0,他引:2  
BACKGROUND: We evaluated the electrical activity of the corpus cavernosum after intracavernous papaverine injection in rats that had been denervated experimentally. METHODS: Twenty-four male adult Sprague Dawley rats were divided into three groups: (i) controls (n=8) (ii) unilateral cavernous nerve resection on the right side (n=8); and (iii) bilateral cavernous nerve resection (n=8). Through a suprapubic incision, the urinary bladder was retracted laterally to locate the major pelvic plexus on the lateral surface of the prostate. The major branch of the cavernous nerve, running caudally from the pelvic plexus, was isolated and excised using an operating microscope. Three weeks later, recording of the electrical activity of the corpus cavernosum (EACC) was performed by using a Neuropack-2 EMG unit (Nihon Kohden, Tokyo, Japan) and coencentric needle electrode. Changes in amplitude were evaluated before and after intracavernosal papaverine injection. The results in the flaccid state and after papaverine injection were compared by using the Mann Whitney U-test in all three groups and paired t-test between groups. RESULTS: In the flaccid penis, the mean (+/- SD) amplitude of electrical activity of the corpus cavernosum was 17.42+/-2.05, 12.42+/-1.88, 9.71+/-1.59 and 5.85+/-0.96 microV in control rats, in unilaterally denervated rats (in which the cavernous nerve was intact on the left side), in unilaterally denervated rats in which the cavernous nerve was resected on the right side and in bilaterally denervated rats, respectively. In the flaccid state, EACC is lower in the bilaterally denervated group than in the control and unilaterally nerve-resected groups (P < or = 0.05). The recording of electrical activity of the corpus cavernosum was continued for 20 min after papaverine injection. In the control group and in both groups of unilaterally denervated rats, we observed a significant decrease in the electrical activity of the corpus cavernosum in the first 5 min after papaverine injection (P < or = 0.05). However, no difference was observed in bilaterally denervated rats after injection (P > or = 0.05). CONCLUSIONS: We conclude that electrical activity of the corpus cavernosum continues after unilateral nerve injury in rats. Cross-innervation may play a role in penile innervation and corpus cavernosum electromyography shows electrical activity in denervated rats.  相似文献   

10.
In this study, we have characterized functional EP receptors in human corpus cavernosum (HCC) tissue and in HCC smooth muscle cells (SMC). Using RNase protection assays, we determined expression of EP2, EP3I and EP3II receptor mRNA. In organ bath preparations of HCC tissue strips, PGE1 caused dose-dependent relaxation at concentrations below 300 nM. At concentrations greater than 300 nM, PGE1 caused contraction. Addition of the EP1/EP2/EP3 receptor antagonist AH6809 inhibited this contraction and facilitated further relaxation through concentrations above 1 microM of PGE1. The EP1/EP3 receptor selective agonist 17-phenyltrinor-PGE2 caused dose-dependent contraction that was partially attenuated by SC51322, an EP1 selective antagonist. In cultures of HCC SMC, PGE1 stimulated cAMP accumulation in a dose-dependent manner. Interestingly, AH6809 significantly attenuated PGE1-induced cAMP accumulation. Sulprostone, a selective EP3 receptor agonist, induced weak contractions in HCC tissue strips but augmented forskolin-induced cAMP synthesis in HCC SMC. The data in this study suggest that HCC and cultured smooth muscle cells express EP1, EP2 and EP3 receptors. These receptors mediate their responses via different biochemical pathways and are expected to have different responses in regulating smooth muscle tone. Thus, we suggest that the ultimate response in erectile tissue to various prostanoids is the integration of responses elicited by individual EP receptor subtypes to a given ligand.  相似文献   

11.
Penile trabecular smooth muscle tone, a major determinant of erectile function, is highly regulated by numerous inter- and intracellular pathways. The interaction between pathways mediating contraction and relaxation has not been studied in detail. To this end, we investigated the functional effects of alpha adrenergic receptor blockade with phentolamine and its interaction with vasodilators (sildenafil, vasoactive intestinal polypeptide (VIP) and PGE1) that elevate cyclic nucleotides on penile cavernosal smooth muscle contractility. In organ bath preparations of cavernosal tissue strips contracted with phenylephrine, phentolamine significantly enhanced relaxation induced by sildenafil, VIP and PGE1. Sildenafil, VIP or PGE1 also significantly enhanced relaxation induced by phentolamine in cavernosal tissue strips contracted with phenylephrine. To study the effects of alpha adrenergic receptor blockade and modification of cyclic nucleotide metabolism during active neurogenic input, cavernosal tissue strips in organ bath preparations were contracted with the non-adrenergic agonist endothelin-1 and subjected to electrical field stimulation (EFS) in the absence or presence of phentolamine and/or sildenafil. EFS (5-40Hz) typically caused biphasic relaxation and contraction responses. Phentolamine alone enhanced relaxation and reduced or prevented contraction to EFS. Sildenafil enhanced relaxation to EFS at lower frequencies (< or = 5 Hz). The combination of phentolamine and sildenafil enhanced EFS-induced relaxation at all frequencies tested. EFS, in the presence of 10 nM phentolamine and 30 nM sildenafil, produced enhanced relaxation responses which were quantitatively similar to those obtained in the presence of 50 nM sildenafil alone. Thus, blockade of alpha-adrenergic receptors with phentolamine increases the efficacy of cyclic nucleotide-dependent vasodilators. Furthermore, phentolamine potentiates relaxation and attenuates contraction in response to endogenous neurotransmitters which are released during EFS. These findings suggest that antagonism of alpha-adrenergic signaling enables other independent relaxatory pathways to predominate within penile trabecular smooth muscle.  相似文献   

12.
The erectile tissue from 15 normal and impotent male patients was studied by electron microscopy to determine if any ultrastructural features could contribute to the basic understanding of the physiology of penile erection and detumescence. It was found that the endothelium lining the cavernous lacunae contained both contractile elements and Weibel-Palade bodies which have a possible role in vasoconstriction. Within the trabeculae of the cavernous body there was an abundance of elastin as well as oxytalan and elaunin fibers around bundles of smooth muscle. With these elements affording an anchorage system for contraction of smooth muscles within the trabeculae, an alternate contraction of smooth muscles and endothelium could account for the erectile and detumescent states.  相似文献   

13.
The neurotransmitters and vasoactive substances regulating tone in the smooth muscle of the penile arteries/arterioles and the trabeculae of the corpora cavernosa are critical mediators of the state of penile erection. Contemporary research reveals a coordinated, intricate interplay between the pathways of vasorelaxation and vasoconstriction representing a most efficient physiological mechanism to initiate and maintain penile erection. This paper will focus on the role of the adrenergic constrictor pathways in penile erection and, more specifically, on the pre-junctional adrenergic mechanisms that regulate smooth muscle constriction. All neurogenic constrictor responses are related to the release of norepinephrine from adrenergic nerves that act on post-junctional alpha-1 and pre-junctional and post-junctional alpha-2 receptor subtypes. Based on the current state of knowledge, there are at least three pre-junctional mechanisms regulating penile smooth muscle tone. First, norepinephrine release from the adrenergic nerves binds to the pre-junctional alpha-2 adrenoceptor on the adrenergic nerves and negatively regulates norepinephrine release. Blockade of this reaction by selective alpha-2 receptor antagonists (e.g. yohimbine or delequamine) will enhance norepinephrine release. Second, norepinephrine release from the adrenergic nerves binds to the pre-junctional alpha-2 adrenoceptor on the non-adrenergic, non-cholinergic (NANC) nerves and inhibits nitric oxide synthesis and release. Blockade of this reaction by selective alpha-2 receptor antagonists (e.g. yohimbine or delequamine) will enhance nitric oxide release, facilitating erection. Finally, cholinergic nerves pre-junctionally inhibit norepinephrine release from the adrenergic nerve and stimulate the NANC nerve to increase nitric oxide synthesis and release. These observations indicate that different neurotransmitters regulate the adrenergic neurotransmission pathway. Based on the above concepts for pre-junctional and post-junctional regulation of smooth muscle tone, the most efficacious strategy to reduce adrenergic activity and facilitate penile erection is to combine alpha-1 and alpha-2 adrenergic receptor antagonists. In this case, any enhancement of norepinephrine release is of little importance because the alpha-1 receptor antagonist will impede this vasoconstrictor response. This will also enhance the release of nitric oxide, which increases smooth muscle relaxation and decreases contraction resulting in penile erection.  相似文献   

14.
15.
16.
Rupture of the corpus cavernosum is a rare but probably under-reported entity. It truly represents a urological emergency and current recommendations are for early surgical intervention. We review 5 cases with evaluation, treatment and followup. Delays in treatment lead to long-term complications, such as erectile dysfunction and penile curvature.  相似文献   

17.
目的 观察大鼠阴茎海绵体肌源性干细胞(MDSCs)在血管内皮细胞生长因子(VEGF)和碱性成纤维细胞生长因子(bFGF)共同作用下向内皮细胞分化的潜能.方法 采用Preplate差速贴壁法结合密度梯度离心法分离、纯化大鼠阴茎海绵体MDSCs,获得差速贴壁细胞(PP1-PP6),免疫荧光细胞化学法检测PP6细胞干细胞抗原-l(Sca-1)和结蛋白(Desmin)的表达,并传代培养.取PP6第3代细胞在VEGF和bFGF共同诱导21 d后,免疫荧光细胞化学法鉴定内皮细胞标志物[CD31、胎肝激酶-l(Flk-1)]的表达;分别在诱导0、5、10、15、21 d,通过逆转录-聚合酶链反应(RT-PCR)检测干细胞标志物(Oct-4)和内皮细胞标志物[CD31、内皮型一氧化氮合酶(eNOS)、Flk-1] mRNA的表达量;通过Dil-Ac-LDL摄取实验检测细胞吞噬低密度脂蛋白的能力;划痕24h后观察划痕空白处的距离,评估细胞的迁移能力.结果 PP6细胞表达肌源性干细胞标志物Sca-1和Desmin;PP6诱导21 d后表达内皮细胞标志物(CD31和Flk-1),诱导21 d后与诱导0d比较,干细胞标志物Oct-4的mRNA表达量下降(下降倍数为0.445±0.025),而内皮细胞标志物mRNA表达量升高(CD31、eNOS、Flk-1升高倍数分别为2.541±0.146、2.364±0.175、2.538±0.100),差异均有统计学意义(P<0.05).Dil-Ac-LDL摄取实验提示诱导后的细胞具有吞噬低密度脂蛋白的能力;划痕实验观察到诱导组空白处距离为282.01±3.84,未诱导组空白处距离为450.35±1.86,差异有统计学意义(P<0.05).结论 大鼠阴茎海绵体MDSCs在VEGF和bFGF的共同诱导下可分化为内皮细胞,且具有成熟内皮细胞的功能.  相似文献   

18.
19.
目的:内源性硫化氢(H2S)是新发现的气体信号分子,对于平滑肌细胞的舒张具有重要的调节功能。本文探讨糖尿病(DM)大鼠阴茎海绵体组织H2S信号通路及其与DM勃起功能障碍(ED)的关系。方法:8周龄健康雄性SD大鼠20只,随机分成4组:正常对照4周组(A)、DM 4周组(B)、正常对照6周组(C)、DM 6周组(D)。采用腹腔注射链脲佐菌素(50 mg/kg)制作DM模型,对照组给予等量生理盐水腹腔注射。测定各组大鼠阴茎海绵体内压/平均颈动脉压(ICPmax/MAP),取阴茎标本测定组织内H2S浓度、免疫组化和Western印迹检测阴茎海绵体组织内胱硫醚-β-合成酶(CBS)和胱硫醚-γ-裂解酶(CSE)蛋白含量。结果:电压5V和7 V刺激盆神经节测定ICPmax/MAP比值,B组(0.19±0.03,0.29±0.04)较A组(0.46±0.07,0.68±0.09),D组(0.14±0.04,0.25±0.04)较C组(0.43±0.07,0.65±0.16)均显著降低(P0.05)。各组大鼠血清睾酮水平比较,B组[(359.08±60.06)ng/dl]与A组[(469.19±126.46)ng/dl]比较无显著差异性(P0.05),D组血清睾酮水平[(297.01±96.58)ng/dl]与C组[(470.44±209.28)ng/dl]比较无显著差异性(P0.05)。血浆及阴茎组织内H2S浓度,B组较A组、D组较C组均显著降低(P均0.05)。阴茎海绵体组织内CBS和CSE蛋白表达量,B组较A组、D组较C组均显著降低(P0.05),D组较B组亦显著降低(P0.05)。结论:DM大鼠阴茎海绵体内H2S浓度降低、CBS和CSE表达下降,提示H2S信号系统可能与DM的ED病理机制相关。  相似文献   

20.
The aim of this study was to investigate the relationship between sulphur dioxide (SO2) signalling pathway and the changes in erectile function under low androgen levels. Thirty‐six healthy male Sprague Dawley (SD) rats aged eight weeks were randomly divided into androgen replacement group, castration group and sham group. Rats in the androgen replacement group were subcutaneously injected with testosterone propionate at 3 mg/kg every other day postcastration. The maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP) and the relative content of SO2 in the penile corpus cavernosum were measured. The mRNA and protein expressions of aspartate aminotransferase (AAT1 and AAT2), cysteine oxidase (CDO), endothelial nitric oxide synthase (eNOS) and phosphorylation of endothelial nitric oxide synthase (P‐eNOS) were detected. ICPmax/MAP, P‐eNOS/eNOS and the level of SO2 decreased significantly in the castration group compared to the other groups (p < 0.05). The expressions of mRNA and protein decreased significantly in the castration group compared to the androgen replacement group and the sham group (p < 0.05), while there was no significant difference between the androgen replacement group and sham group. Low androgen levels can inhibit erectile function by downregulating the SO2 signalling pathway.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号