Immunohistochemical Expressions of Main PGE(2) Biosynthesis-related Enzymes and PGE(2) Receptor in Rat Nephrogenesis

Endogenous prostaglandin (PG) E(2) plays important roles in renal homeostasis. Immunoexpressions of PGE(2) biosynthesis-related enzymes, cyclooxygenase (COX)-2 and microsomal PGE(2) synthetase (mPGES)-1 and EP4 (a PGE(2) receptor), were investigated in renal development. Kidney tissues were obtained from fetuses on gestation days 18 and 21 and neonates on days 1 to 18. In fetuses and early neonates, the expressions of COX-2, mPGES-1 and EP4 were observed in developing renal tubules, indicating that COX-2 and its product, PGE(2), play important roles in blastemal cell-derived renal tubular development via EP4. Cyclin D1 expression was seen in both the nucleus and cytoplasm of the developing tubules. These findings differed from the decreased COX-2 expression and exclusive nuclear expression of cyclin D1 seen in abnormal epithelial regeneration of injured renal tubules in cisplatin-treated rats in our previous articles. Collectively, PGE(2), induced by COX-2, regulates renal tubular epithelial formation via EP4.     

Canine renal pathology associated with grape or raisin ingestion: 10 cases.

Ten dogs suffered acute renal failure after ingesting > or = 3 g/kg (dry matter) of grapes or raisins. All dogs had degeneration or necrosis (or both) of proximal renal tubules with basement membranes remaining intact, and epithelial regeneration was observed in 5 out of 10 cases. Mineralized tubular debris or granular to proteinaceous casts (or both) were present in all cases. A golden-brown, globular, intracellular pigment of varying amounts and sizes was observed in 6 out of 10 cases with variable reaction with Prussian blue. Multifocal fibrinous arteritis of the large colon was seen in 2 out of 5 cases with globulin insudation of vessel wall demonstrated by immunohistochemical staining for immunoglobulin (Ig)G and IgM. Mineral analysis on frozen renal tissue from 2 out of 2 cases revealed mildly elevated Ca:P ratio in both. Clinically significant observations were preservation of the integrity of basement membranes after grape-induced tubular injury and presence of early epithelial regeneration. Thus, recovery may be possible if anuria is aggressively managed. With respect to potential pathophysiologic mechanisms, further research into the roles of calcium homeostasis, vascular reactivity, and the significance of the golden-brown pigment is indicated.     

Cell-cycle-dependent Colonization of Mouse Spermatogonial Stem Cells After Transplantation into Seminiferous Tubules

Spermatogonial stem cells (SSCs) migrate to the niche upon introduction into the seminiferous tubules of the testis of infertile animals. However, only 5–10% of the transplanted cells colonize recipient testes. In this study, we analyzed the impact of cell cycle on spermatogonial transplantation. We used fluorescent ubiquitination-based cell cycle indicator transgenic mice to examine the influence of cell cycle on SSC activity of mouse germline stem (GS) cells, a population of cultured spermatogonia enriched for SSCs. GS cells in the G1 phase are more efficient than those in the S/G2-M phase in colonizing the seminiferous tubules of adult mice. Cells in the G1 phase not only showed higher expression levels of GFRA1, a component of the GDNF self-renewal factor receptor, but also adhered more efficiently to laminin-coated plates. Furthermore, this cell cycle-dependency was not observed when cells were transplanted into immature pup recipients, which do not have the blood-testis barrier (BTB) between Sertoli cells, suggesting that cells in the G1 phase may passage through the BTB more readily than cells in the S/G2-M phase. Thus cell cycle status is an important factor in regulating SSC migration to the niche.     

玉米赤霉烯酮对小鼠胸腺上皮细胞的毒性作用

采用台盼蓝计数、流式细胞仪分析等方法,离体研究玉米赤霉烯酮对小鼠胸腺上皮细胞增殖与细胞周期的影响,结果发现:不同质量浓度(1～25 mg/L)玉米赤霉烯酮对小鼠胸腺上皮细胞的增殖均具有显著抑制作用(P<0.05),并表现出与剂量和处理时间依赖性关系.高剂量(10～25 mg/L)ZEA使小鼠胸腺上皮细胞细胞周期显著阻滞于G2/M期(P<0.05),并存在剂量依赖性关系.这些结果表明,玉米赤霉烯酮对小鼠胸腺上皮细胞有直接毒害作用.     

A case report of a renal mixed epithelial and stromal tumor in a heterozygous S1P2 receptor deficient mouse

We report a case of mixed epithelial and stromal tumor of the kidney (MESTK) in a 32-week-old heterozygous sphingosine 1-phosphate-2 (S1P2) receptor deficient female mouse. A white solid mass replacing the left kidney was observed at the left retroperitoneal wall. Histologically, the tumor mass consisted of dimorphic cellular components of epithelial and stromal cells. Epithelial cells formed various sized irregular-shaped tubular structures resembling renal tubules surrounded by stromal cells. Immunohistochemically, epithelial cells were positive for cytokeratin, while stromal cells showed positive immunoreactivity with alpha-smooth muscle actin as well as vimentin. Based on the morphological and immunohistochemical findings, this tumor was diagnosed as a MESTK.     

Low expression of cyclin D2 in G2/M-arrested and transformed proliferating Balb/3T3 cells

At present, the effect of cyclin D2 implicated in cell cycle regulation, differentiation, and oncogenic transformation is not fully confirmed. To better elucidate the role of cyclin D2 in controling the cell proliferation, cyclin D2 expression level was determined at the early initiation and promotion stages during the in vitro two-stage transformation process of Balb/3T3 A31 cells. N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced G2/M-arrested cells expressed low level of cyclin D2 mRNA, while the contact-inhibited nonproliferating cells expressed high level of cyclin D2 mRNA. In the transformed proliferating cells at the promotion stage, cyclin D2 mRNA was not expressed. These data suggest that cyclin D2 expression may be associated with the type of growth arrest and nonproliferating state, but not with the cell proliferation and transformation.     

Tumor necrosis factor-α inhibits the stimulatory effect of luteinizing hormone and prostaglandin E(2) on progesterone secretion by the bovine corpus luteum

Tumor necrosis factor-α (TNF-α) is involved in the tissue remodeling that occurs in the corpus luteum (CL) during its development and regression. This cytokine is also implicated in the regulation of reproduction by its actions on ovarian steroidogenic cells. The aim of this study was to examine the influence of TNF-α on (1) progesterone (P(4)) output by the bovine CL and on (2) the responsiveness of the CL to LH or prostaglandin E(2) (PGE(2)) in vitro. In experiment 1, CL (days 8 to 10 of the estrous cycle) were perfused by using an in vitro microdialysis system with TNF-α (0.1, 0.5, or 1 μg/mL) alone or with TNF-α (1 μg/mL) followed by LH (1000 ng/mL) or PGE(2) (2 × 10(-5) M). Basal P(4) release (P < 0.05) was increased by TNF-α (0.5 or 1 μg/mL). Moreover, TNF-α (1 μg/mL) inhibited the stimulatory effect of LH or PGE(2) on P(4) output (P < 0.05). In experiment 2, 4 h after intrauterine infusion of TNF-α (0.01 μg/mL or 1 μg/mL), CL (days 8 to 10 of the estrous cycle) were collected by colpotomy, cultured, and stimulated with LH (10 ng/mL) or PGE(2) (10(-6) M). Intrauterine infusion of TNF-α at a concentration of 1 μg/mL increased basal P(4) output by CL (P < 0.05). Moreover, the intrauterine infusion of TNF-α at a concentration of 0.01 μg/mL inhibited the stimulatory effect of LH or PGE(2) on P(4) output (P < 0.05). These results indicate that TNF-α (1) does not have an effect on the autonomous, pulsatile release of P(4); (2) increases P(4) secretion by bovine CL with increasing doses, and (3) reduces in a dose-dependent manner the responsiveness of CL to luteotropic factors both directly (after infusion to CL) and indirectly (after intrauterine infusion).     

Histological and ultrastructural studies of renal lesions in Babesia canis infected dogs treated with imidocarb

Histological and electron microscopic examinations of the kidneys of 8 dogs suffering from fatal, naturally acquired Babesia canis infection and nephropathy are presented. Seven animals were treated with imidocarb dipropionate on average 4.5 days prior to death. Severe anaemia was present only in 2 cases. Degenerative histological changes observed mostly in the proximal convoluted tubules included vacuolar-hydropic degeneration, necrosis and detachment of renal tubular epithelial (RTE) cells from the basement membrane. Necrotic debris occasionally formed acidophilic casts within the tubules. In some cases, necrosis of the whole tubule was observed. Haemoglobin casts in the tubules and haemoglobin droplets in RTE cells seldom appeared. No significant histological changes were seen in the glomeruli. Ultrastructural lesions in RTE cells included nuclear membrane hyperchromatosis, karyopyknosis, karyolysis, swelling or collapse of mitochondria with fragmentation of cristae and vacuolar-hydropic degeneration in the endoplasmic reticulum and microvilli. Nuclear oedema was also observed. Many RTE cells exhibiting necrosis collapsed. Vacuolar-hydropic degeneration and necrosis were also observed in the glomerular and interstitial capillary endothelium. The severe acute tubular necrosis described in this study is probably the result of hypoxic renal injury. Systemic hypotension leading to vasoconstriction in the kidneys might be the most important cause of renal hypoxia in B. canis infections, but anaemia may also contribute to inadequate oxygenation. Imidocarb should be applied with caution in patients with possible renal involvement until further data become available on its potential nephrotoxicity in dogs.     

磺胺类药物对猪肾脏损害的病理学观察

对14例含有磺胺结晶的猪肾脏用10%中性福尔马林固定,常规石蜡切片技术切片染色,对肾脏进行组织病理学观察。结果显示,皮质区肾小管上皮细胞肿胀变性、髄质区肾小管破坏较为严重,大部分肾小管、集合管上皮细胞脱落、变性坏死,并引起梗阻性肾病,同时,肾小球囊腔扩张、血管球萎缩。结果证实,超剂量或长期使用磺胺类药物会严重损害肾实质,导致肾功能下降甚至肾衰竭。     

Prostaglandins F2α and E2 Secretion by Porcine Epithelial and Stromal Endometrial Cells on Different Days of the Oestrous Cycle

The endometrial tissue of the uterus plays a key role in reproduction and is a source of hormones and factors responsible for the proper physiological function of reproductive tract during the oestrous cycle and pregnancy. In this study, we investigated the pattern of PGF(2alpha) and PGE(2) secretion from cultured porcine endometrial cells at different days of the oestrous cycle. Epithelial and stromal cells were isolated by differential enzymatic digestion on days 6-8, 10-12 and 14-16. After attachment cells were incubated for 3 and 24 h to estimate PGF(2alpha) and PGE(2) output. The purity of culture was 85-90% for epithelial and 95-98% for stromal cells as determined by immunofluorescent staining. Release of PGF(2alpha) and PGE(2) was affected by cell type, days of the oestrous cycle and the time of incubation. After 3 h of incubation epithelial cells secreted more PGF(2alpha) than PGE(2) during all studied periods of the oestrous cycle (p < 0.01 and p < 0.001, respectively), whereas stromal cells released more PGE(2) (p < 0.01) on days 10-12 and 14-16. Longer incubation of stromal cells revealed that PGF(2alpha) output tended to overcome PGE(2) on days 10-16. The lowest secretion of prostaglandins was observed on days 6-8 in both cell types. The highest secretion of PGF(2alpha) from epithelium was measured on days 10-12 after 24 h of incubation when compared with other days studied (p < 0.001). In stromal cells, PGE(2) output increased on consecutive days studied (p < 0.001) after 3 h of incubation. The differential properties of endometrial cell types seem to play an important role in the profile of PGF(2alpha) and PGE(2) release before and during luteolysis. Described endometrial cells culture might serve as the model for further studies on the hormonal regulation of prostaglandin production in the pig.     

Renal Tubular Cyst Formation in Newborn Rats Treated with p-Cumylphenol

In this study, we investigated the sequential changes in the development of renal tubular cysts in newborn rats treated with p-cumylphenol (PCP). Fifteen animals per sex were treated orally with 300 mg/kg/day of PCP for up to 18 days from postnatal day (PND) 4 and were sacrificed on PNDs 8, 12, 19 and 22 and after a 7 day recovery period. On PNDs 8 and 12, slight dilatation of the collecting ducts was frequently observed in the medulla and slight papillary necrosis was also noted in some cases. These dilated collecting ducts were lined with slightly hyperplastic epithelial cells. On PNDs 19 and 22, multiple large cystic changes arising from the collecting ducts in the outer medulla were seen. These cystically dilated ducts were also lined with hyperplastic epithelial cells. During the dosing period, the labeling index of proliferating cell nuclear antigen in the collecting duct epithelium was higher in the PCP-treated group than in the control group at all time points. After a 7 day recovery period, the cystic change still remained, although the cell density was decreased and the epithelial cells became flattened. On the other hand, basophilic tubules with peritubular lymphoid cell infiltration were multifocally observed in the cortex. In conclusion, PCP induced multiple renal cysts that developed in the collecting ducts of the outer medulla in neonatal rats, and it is suggested that epithelial cell proliferation may play some roles in the induction of cystic lesions.     

犊牛磺胺中毒的病理形态学观察

为了解犊牛磺胺中毒的病理形态学变化特点,对2头因磺胺中毒而死亡的犊牛进行了详细的病理学研究.结果表明,犊牛磺胺中毒的病理性损伤主要发生于肾脏和肝脏.宏观检查可见,肾脏肿胀,色泽变淡,皮质增宽,肾盂有多量豆腐渣样物质.肝脏肿胀,淡橘红色,质地脆易碎.微观检查可见,近曲小管上皮细胞肿胀,核浓缩,染色不良,大量上皮细胞脱落....     

COX‐2, mPGES‐1 and EP2 receptor immunohistochemical expression in canine and feline malignant mammary tumours

Prostaglandin (PG) signalling is involved in human and animal cancer development. PG E₂ (PGE₂) tumour‐promoting activity has been confirmed and its production is controlled by Cyclooxygenase‐2 (COX‐2) and microsomal PGE synthase‐1 (mPGES‐1). Evidence suggests that mPGES‐1 and COX‐2 contribute to carcinogenesis through the EP2 receptor. The aim of our study was to detect by immunohistochemistry COX‐2, mPGES‐1 and EP2 receptor expression in canine (n = 46) and feline (n = 50) mammary tumours and in mammary non‐neoplastic tissues. COX‐2 positivity was observed in 83% canine and 81% feline mammary carcinomas, mPGES‐1 in 75% canine and 66% feline mammary carcinomas and the EP2 receptor expression was observed in 89% canine and 54% feline carcinomas. The frequency of COX‐2, EP2 receptor and mPGES‐1 expression was significantly higher in carcinomas than in non‐neoplastic tissues and adenomas. COX‐2, mPGES‐1 and EP2 receptor expression was strongly associated. These findings support a role of the COX‐2/PGE2 pathway in the pathogenesis of these tumours.     

鸡贮精腺上皮细胞的分离及原代培养

试验旨在探讨稳定可靠的贮精腺上皮细胞分离及原代培养方法,为研究鸡贮精机理提供细胞模型。以鸡输卵管的子宫阴道交接部组织样为材料,采用酶消化法和组织块培养法分离培养母鸡贮精腺上皮细胞,观察母鸡贮精腺上皮细胞的培养情况,比较不同细胞培养方法获得贮精腺上皮细胞的生长情况。结果表明,用胶原酶或胰酶单独消化母鸡子宫阴道交接部组织,经100目过滤后获得的贮精腺上皮细胞24 h后可贴壁,但48～72 h后细胞死亡;用胶原酶Ⅺ(0.01 g/mL)与胰酶(0.25%)先后消化母鸡子宫阴道交接部组织后再经100目过滤获得的贮精腺上皮细胞贴壁性良好,24～48 h细胞出现明显增殖,72 h后细胞增殖速度减慢,开始死亡;用组织块培养法7 d可获得鸡贮精腺上皮原代细胞,该细胞可传2～3代;用组织块培养法获得的细胞进行免疫组化试验,发现细胞表达贮精腺差异表达基因编码的NXPH1蛋白,该蛋白在培养细胞内的表达符合其分泌蛋白特性,表明组织块培养法所获细胞可用于后续研究。综上,用组织块培养法获得的鸡贮精腺上皮细胞可为研究母鸡贮精腺机制提供细胞模型。     

Effect of dihydrotestosterone on mouse embryonic stem cells exposed to H2O2-induced oxidative stress

Oxidative stresses induced by reactive oxygen species (ROS) have been shown to be involved in several physiological and pathophysiological processes, such as cell proliferation and differentiation. Steroid hormones can protect cells against apoptosis or induce cell proliferation by several mechanisms. Among androgenic hormones, dihydrotestosterone (DHT) is generated by a 5α-reduction of testosterone. Unlike testosterone, DHT cannot be aromatized to estradiol, therefore DHT is considered a pure androgenic steroid. This study was conducted to examine the effect of DHT (10^-7 M) on H₂O₂ (10^-3 M) -induced injuries in mouse embryonic stem (ES) cells. H₂O₂ induced ROS generation and increased lipid peroxide formation and DNA fragmentation. These effects of H₂O₂ were inhibited by pretreatment with DHT. H₂O₂ also increased the phosphorylation of p38 MAPK, SAPK/JNK and nuclear factor kappa B (NF-κB), but DHT blocked these effects. Moreover, H₂O₂ decreased DNA synthesis and the levels of cell cycle regulatory proteins [cyclin D1, cyclin E, cyclin-dependent kinase (CDK) 2, and CDK 4]. These effects of H₂O₂ were inhibited by pretreatment with DHT. In conclusion, DHT may partially prevent H₂O₂-induced cell injury through inhibition of ROS and ROS-induced activation of p38 MAPK, SAPK/JNK and NF-κB in mouse ES cells.     

Effects of 2-chloro-4-acetotoluidine (CAT) toxicity on biochemical and morphological alterations in quail

Morphological changes in response to 2-chloro-4-acetotoluidine (CAT) toxicity in the quail appeared in the form of progressive necrosis of the kidney, particularly the proximal tubular epithelial cells. Changes at 32 hr after the CAT administration included vacuolar degeneration, dilatation of distal tubules containing hyaline and granular casts, overt necrosis, and deposition of urate casts in collecting tubules. There were no striking histopathological changes in the liver at 24 hr. However, small focal necrotic lesions were seen 32 hr after the CAT administration. A 40% protection against the toxicity of CAT at the lower dose was seen in quail pretreated with phenobarbital. The protection offered by phenobarbital pretreatment was attributed to a quantitative shunting of CAT and/or its reactive metabolite along the microsomal-mediated metabolic pathway of the kidney responsible for their inactivation. Administration of reduced glutathione (GSH) to quail treated with CAT offered little protection against the toxicity. The quail treated with a toxic dose of CAT had an increased level of thiobarbituric acid (TBA) reacting products in the liver, with a concomitant decrease in GSH content. This suggests that lipid peroxidation may be involved in CAT-induced hepatic damage of quail. It was hypothesized that the depletion of protective GSH stores coincident with gradual shutdown of the protective peroxidase system of the kidney may occur in a more advanced stage of CAT toxicity in quail. This would then result in a severe disturbance in renal excretion of uric acid and in frank necrosis of renal tubules.     

Butyrate-induced apoptosis and cell cycle arrest in bovine kidney epithelial cells: involvement of caspase and proteasome pathways

Beyond their nutritional effect, short-chain fatty acids, especially butyrate, modulate cell differentiation, proliferation, motility, and in particular, they induce cell cycle arrest and apoptosis. A bovine kidney epithelial cell line (Madin-Darby bovine kidney; MDBK) was used to investigate the cell cycle regulatory and apoptotic effects of butyrate. Butyrate not only induced apoptosis but also induced cell cycle arrest at the G1/S boundary and M/G2 in MDBK cells (P < 0.01). The cell responses were concentration-dependent (r(2) = 0.9482, P <0.001). In examining possible mechanisms for the apoptosis and cell cycle arrest induced by butyrate, the results showed that butyrate treatment activates caspase-3 activities and induces accumulation of acetylated histone. At least two proteins, cdc6 and cdk1, become targeted for destruction on butyrate treatment. These two proteins are downregulated (P < 0.01 and P < 0.05, respectively) by proteolytic pathways. Moreover, the proteasome inhibitor MG-132 (carbobenzoxy-L-leucyl-L-leucyl-L-leucinal) reverses the cell cycle arrest induced by butyrate, indicating a multiprotein crosstalk wherein the ubiquitination/ proteasome pathway interacted with the caspase-signaling pathway. Because the proteasome inhibitor MG-132 blocked activation of caspase-3, these results functionally locate the proteasome pathway upstream of the caspase pathway. All these results indicate that butyrate functions as both a nutrient and signaling molecule regulating cell growth and proliferation.     

Expression of Heparin‐Binding EGF‐Like Growth Factor (HB‐EGF) in Bovine Endometrium: Effects of HB‐EGF and Interferon‐τ on Prostaglandin Production

Heparin‐binding EGF‐like growth factor (HB‐EGF) regulates several cell functions by binding to its membrane receptor (ErbB1 and ErbB4). Experimental evidences suggest that HB‐EGF, prostaglandins (PGs) and interferon‐τ (IFN‐τ) regulate uterine function for pregnancy establishment in ruminants. In this study, the mRNA expressions of HB‐EGF, ErbB1 and ErbB4 in bovine endometrium and the effects of HB‐EGF and IFN‐τ on PGE2 and PGF2‐α production by endometrial cells were investigated. RT‐PCR analysis revealed that HB‐EGF mRNA was greater at the mid‐luteal stage than at the early and regressed luteal stages (p < 0.05). ErbB1 mRNA expression was greater at the mid‐ and late luteal stages than at the other luteal stages (p < 0.05). IFN‐τ increased the expression of HB‐EGF, ErbB1 and ErbB4 mRNA in epithelial cells (p < 0.05). HB‐EGF did not affect PGF2‐α or PGE2 production by bovine endometrial epithelial cells, but increased PGF2‐α and PGE2 production by bovine endometrial stromal cells (p < 0.05). IFN‐τ significantly decreased HB‐EGF‐stimulated PGF2‐α (p < 0.05), but not PGE2 (p > 0.05) production by stromal cells. These results indicate that HB‐EGF and its receptors expression changed in bovine endometrium throughout the oestrous cycle. IFN‐τ increased their expression in cultured endometrial cells. HB‐EGF and IFN‐τ have the ability to regulate PGs production by stromal cells and therefore may play a role in the local regulation of uterine function at the time of implantation in cattle.     

Inactivation of the Wnt/β-catenin signaling contributes to the epithelial barrier dysfunction induced by sodium oxalate in canine renal epithelial cells

High oxalate consumption has been recognized as a risk factor for renal calcium oxalate stones in companion animals (dogs and cats). However, the cellular signaling involved in oxalate-induced dysfunction in renal tubular epithelial cells remains not fully elucidated. In this study, Mardin–Darby canine kidney (MDCK) cells, an epithelial cell line derived from canine kidney tubule, were tested for cell proliferation activity and barrier function after being exposed to sodium oxalate (NaOx). Further, the involvement of Wnt/β-catenin in NaOx-induced renal epithelial barrier dysfunction was evaluated. MDCK cells treated with NaOx exhibited reduction in cell proliferation and migration. Besides, NaOx exposure led to a decrease in transepithelial electrical resistance and an increase in paracellular permeability. The deleterious effects of NaOx on epithelial barrier function were related to the suppressed abundance of tight junction proteins including zonula occludens, occludin, and claudin-1. Of note, protein levels of β-catenin and phosphorylated (p)-β-catenin (Ser552) in MDCK cells were repressed by NaOx, indicating inhibitory effects on Wnt/β-catenin signaling. An inhibition of glycogen synthase kinase-3β (GSK-3β) by SB216763 enhanced the abundance of β-catenin and p-β-catenin (Ser552), and protected against epithelial barrier dysfunction in NaOx-treated MDCK cells. The results revealed a critical role of Wnt/β-catenin signaling in the epithelial barrier function of MDCK cells. Activation of Wnt/β-catenin signaling might be a potential therapeutic target for the treatment of oxalate-linked renal stones.     

EP2受体激动剂Butaprost对奶牛子宫内膜上皮细胞中血管内皮生长因子基因表达的影响

[目的]观察EP2受体激动剂Butaprost对奶牛子宫内膜上皮细胞中血管内皮生长因子(vascular endothelial growth factor,VEGF)基因表达的影响,探讨前列腺素类化合物对奶牛子宫内膜组织修复的机制。[方法]分离培养奶牛子宫内膜上皮细胞,采用荧光定量PCR技术检测EP2受体激动剂Butaprost对奶牛子宫内膜上皮细胞中VEGFmRNA表达的影响。[结果]10-6mol/L的Butaprost作用于奶牛子宫内膜上皮细胞4、8、16、24h可显著(P<0.05)或极显著(P<0.01)地促进VEGFmRNA的表达。[结论]EP2受体激动剂Butaprost能够促进奶牛子宫内膜上皮细胞中VEGF基因的表达。