Application and enlightenment of formative assessment in the innovation and development of higher education in basic medical science / 生理学报

Formative assessment aims at cultivating and improving students' comprehensive qualities and abilities. It acquires and analyzes the dynamic changes of students' learning process through flexible and diverse assessment methods. The assessment contents cover multiple aspects including knowledge, abilities, attitudes, literacy, etc., which help teachers and students to formulate practical and efficient improvement strategies and to meet the inherent needs of students for comprehensive development. This review describes the connotation of formative assessment and summarizes its application in higher education of basic medical science in China. The existing shortcomings and the reasonable advice are proposed. We also introduce our experience in the application of formative assessment in pathophysiology education. This review will provide reference and enlightenment for the reform and innovation of the assessment system in higher education of basic medical science.

Role and mechanism of muscarinic acetylcholine receptor in the regulation of submandibular gland secretion / 北京大学学报(医学版)

Muscarinic acetylcholine receptors (mAChRs), including M1-M5 subtypes, are classic receptors in regulating water, ion, and solute transport in salivary gland. Our work focuses on the studies on the expression pattern and function of mAChR in the submandibular gland (SMG), and the underlying mechanism involved in the mAChR-regulated secretion, together with the effect of parasympathectomy on the salivary secretion. Microvascular autotransplantation of SMG into the temporal fossa provides a continuous and endogenous source of fluids, and is currently an effective method for treating severe keratoconjunctivitis sicca. By using RT-PCR, Western blotting, and immunofluorescence, our data demonstrated that the expression of M1 and M3 subtypes were decreased in latent period in rabbit SMG autotransplantation model, whereas carbachol stimulation promoted the salivary secretion, as well as M1 and M3 expressions. By contrast, mAChRs were hypersensitive in epiphora SMGs, whereas atropine gel and botulinum toxin A application significantly inhibited the hypersecretion in both animal models and patients. Furthermore, the possible intracellular signal molecules involved in the mAChR-modulated salivary secretion were explored. Activation of mAChR upregulated the expression of aquaporin 5 (AQP5), the main transporter that mediated water secretion through transcellular pathway, and led to AQP5 trafficking from lipid rafts to non-lipid microdomain. Extracellular signal-regulated kinase 1/2 (ERK1/2) was involved in the mAChR-regulated AQP5 content. mAChR activation also modulated the expression, distribution, and function of tight junction proteins, and increased paracellular permeability. ERK1/2/β-arrestin2/clathrin/ubiquitin signaling pathway was responsible for the mAChR-regulated downregulation of tight junction molecule claudin-4. Cytoskeleton filamentous actin (F-actin) was also involved in the distribution and barrier function of epithelial tight junctions. Besides, endothelial tight junctions were opened by mAChR agonist-evoked salivation in the mice. Furthermore, parasympathetic denervation increased resting salivary secretion in the long terminrats and minipigs. Taken together, our work demonstrated that mAChR regulated saliva secretion via transcellular and paracellular pathways in SMG epithelium as well as tight junction opening in SMG endothelium. Modulation of mAChR might be a promising strategy to ameliorate SMG dysfunction.

Analysis of the risk factors of radiation-induced caries in patients with head and neck cancer / 华西口腔医学杂志

OBJECTIVE@#This study aimed to evaluate the risk factors of radiation-induced caries by using a multiple linear regression equation and to provide the basis for the effective prevention of radioactive caries.@*METHODS@#A total of 166 patients with head and neck cancer who underwent radiotherapy were selected as subjects. The number of decayed, missing or filled surfaces were recorded. Questionnaire contents included age, sex, radiation dose, and radiotherapy techniques. Multiple stepwise regression analyses were performed to identify the risk factors of radiation-induced caries.@*RESULTS@#Multiple stepwise regression analyses indicated that the main risk factors of radiation-induced caries were plaque index, radiotherapy techniques, time after radiotherapy, and radiotherapy dose.@*CONCLUSIONS@#The awareness of dental care and caries treatment should be improved to reduce the occurrence of radiation-induced caries in patients with head and neck cancer. In addition, intensity modulated radiation therapy should be employed to decrease the radiation exposure dose received by teeth.

Construction of core collection of Psammosilene tunicoides based on polymorphism of β-AS gene / 中国中药杂志

Psammosilene tunicoides is one of the main ingredients of the "Yunnan Baiyao". P. tunicoides is an endangered species included in the secondary protection list in China Plant Red Data Book as well as the endemic species in Southwest China. Its natural resources could not meet the needs of pharmaceutical production. Construction of core collection of P. tunicoides will lay the foundation for germplasm improvement and molecular breeding. The sequence variation of the key enzymes gene locus (β-AS) were carried out to survey the population structure and population history of the species. Among the 11 populations across its geographical range, 36 haplotypes were identified. The levels of haplotype diversity (Hd=0.905) were high, while the levels of population differentiation (GST=0.280) were low. Analysisof molecular variance (AMOVA) indicated that a significantly greater proportion of total genetic variationpartitioned among populations thanwithin populations (values of 77.43% and 22.57%, respectively). These results in combination with the star-like phylogenetic network analysis indicate that Hap1 as an ancestral haplotypewas shared in four populations, Hap2, Hap4, Hap15 and Hap16 are occurred in two populations, the remains as private haplotype only distributed in single population. The strategy of core collection was constructed in order to maximumpreserve genetic diversity of P. tunicoides.

A 20-year study on microvascular autologous transplantation of submandibular gland for treatment of severe dry eye / 北京大学学报(医学版)

Severe dry eye is a refractory ophthalmologic disease. Our multidisciplinary research group treated severe dry eye by microvascular autologous transplantation of submandibular gland (SMG) during the past 20 years. The SMG, with its blood vessels and Wharton's duct, was harvested from the submandibular triangle and transferred to the temporal area. The blood vessels in the SMG were anastomosed with the temporal blood vessels using a microsurgical technique. Then, the distal end of Wharton's duct was sutured to form an opening in the upper lateral conjunctival fold. The tear was replaced by the secretion of the transplanted SMG to lubricate the ocular surface. In our study, the surgical techniques of blood vessel management were continuously modified to increase the survival rate of the transplanted SMG. A novel surgical modality of partial transplantation of SMG was established to prevent postoperative epiphora. A clinical study with the largest case number in the world was conducted and the effectiveness of transplantation of SMG for severe dry eye was fully confirmed. In order to resolve two main clinical problems including ductal obstruction resulted from low secretion rate during the latent period, and epiphora due to over secretion of the transplanted SMG in the later term of transplantation, the regulation of the secretion mechanism of the normal and transplanted SMG were investigated. New opinions on mechanisms of saliva secretion were provided. Based on the priniciple of translational medicine, the results of related basic research were applied in the clinic. The clinical guidelines for secretion regulation of transplanted SMG were established. A concept of chronic obstructive sialadenitis of transplanted SMG was provided and its diagnostic criteria, diagnostic technique of sialography, and therapeutic regimen were established. As a result, the surgical success rate was obviously elevated, the surgical complications were decreased, and life quality of the patients was greatly improved.

Research progress of complement-C1q/tumor necrosis factor-related protein 3 / 生理学报

Complement-C1q/tumor necrosis factor-related protein 3 (CTRP3) is an adipokine that primarily identified in 2003 and is an important member of CTRP family. CTRP3 is expressed in various tissues and cell types, and is highly conserved among different species. Multiple novel functions of CTRP3 have been reported recently as the further research on this protein develops. CTRP3 not only affects the proliferation of chondrocytes and the pathogenesis of osteoarthritis, but also regulates multiple physiological and pathological processes including the secretion of testosterone and adipokines, glucose and lipid metabolism, mitochondrial biogenesis, inflammatory response, cell apoptosis, angiogenesis, vascular calcification and ventricular remodeling. The present review mainly focuses on the research progresses on CTRP3, including its discovery, gene and protein structure, expression regulation, and biological functions. The progresses summarized may provide new clues for the further investigation of CTRP3.

Research progress on the function of epithelial tight junction / 生理学报

Tight junctions (TJs) are widely expressed in the most apical portion of both epithelial and endothelial cell-cell interactions, serving as a structural and functional basis for material transport through the paracellular pathway. TJs are multi-protein complex composed of transmembrane and cytoplasmic proteins. TJs constitute pores allowing materials with specific size and electrical charge to pass through the paracellular pathway, which is so called "barrier" function. Besides, TJs also separate the lumen and interstitial space of epithelium and endothelium by the function of "fence". Recently, there is increasing body of evidence regarding the crucial role of TJs, together with the possible signaling pathways, in many epithelial cells, such as salivary, airway, intestinal and renal epithelial cells. The present review focuses on the latest research progresses on TJs, including TJ's composing, structure, and function measurement, as well as the mechanisms for modulating TJ's functions in some important epithelial cell types. We hope that the review may provide new insight into the therapeutic strategy of epithelium-related disease by targeting TJs.

Visfatin Protects Rat Pancreatic β-cells against IFN-γ-Induced Apoptosis through AMPK and ERK1/2 Signaling Pathways / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Interferon-γ (IFN-γ) plays an important role in apoptosis and was shown to increase the risk of diabetes. Visfatin, an adipokine, has anti-diabetic, anti-tumor, and regulating inflammatory properties. In this study we investigated the effect of visfatin on IFN-γ-induced apoptosis in rat pancreatic β-cells.</p><p><b>METHODS</b>The RINm5F (rat insulinoma cell line) cells exposed to IFN-γ were treated with or without visfatin. The viability and apoptosis of the cells were assessed by using MTT and flow cytometry. The expressions of mRNA and protein were detected by using real-time PCR and western blot analysis.</p><p><b>RESULTS</b>The exposure of RINm5F cells to IFN-γ for 48 h led to increased apoptosis percentage of the cells. Visfatin pretreatment significantly increased the cell viability and reduced the cell apoptosis induced by IFN-γ. IFN-γ-induced increase in expression of p53 mRNA and cytochrome c protein, decrease in mRNA and protein levels of anti-apoptotic protein Bcl-2 were attenuated by visfatin pretreatment. Visfatin also increased AMPK and ERK1/2 phosphorylation and the anti-apoptotic action of visfatin was attenuated by the AMPK and ERK1/2 inhibitor.</p><p><b>CONCLUSION</b>These results suggested that visfatin protected pancreatic islet cells against IFN-γ-induced apoptosis via mitochondria-dependent apoptotic pathway. The anti-apoptotic action of visfatin is mediated by activation of AMPK and ERK1/2 signaling molecules.</p>

Botulinum toxin A inhibits salivary secretion of rabbit submandibular gland / 国际口腔科学杂志·英文版

Botulinum toxin A (BTXA) has been used in several clinical trials to treat excessive glandular secretion; however, the precise mechanism of its action on the secretory function of salivary gland has not been fully elucidated. In this study, we aimed to investigate the effect of BTXA on secretion of submandibular gland in rabbits and to identify its mechanism of action on the secretory function of salivary gland. At 12 weeks after injection with 5 units of BTXA, we found a significant decrease in the saliva flow from submandibular glands, while the salivary amylase concentration increased. Morphological analysis revealed reduction in the size of acinar cells with intracellular accumulation of secretory granules that coalesced to form a large ovoid structure. Expression of M3-muscarinic acetylcholine receptor (M3 receptor) and aquaporin-5 (AQP5) mRNA decreased after BTXA treatment, and distribution of AQP5 in the apical membrane was reduced at 1, 2 and 4 weeks after BTXA injection. Furthermore, BTXA injection was found to induce apoptosis of acini. These results indicate that BTXA decreases the fluid secretion of submandibular glands and increases the concentration of amylase in saliva. Decreased expression of M3 receptor and AQP5, inhibition of AQP5 translocation, and cell apoptosis might involve in BTXA-reduced fluid secretion of submandibular glands.

Effect of parasympathectomy on the salivary secretion of submandibular gland in rats / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of parasympathectomy on secretion of submandibular glands and the feasibility of treatment for xerostomia in rats.</p><p><b>METHODS</b>Twenty Sprague-Dawley male rats weighing 200 - 300 g were randomly divided into the experimental group (n = 12), in which the right chorda-lingual nerve was cut, and the control group (n = 8). The secretion of submandibular gland was measured for 5 min by Schirmer test for both groups.</p><p><b>RESULTS</b>The stimulated saliva flow rate decreased on 1st, 12th and 24th week after denervation in the right operated submandibular glands (P < 0.05). No difference in secretion was found between the left non-operated glands and the control group. Comparing with the left non-operated gland and the control gland, the saliva flow rate at rest in the right operated submandibular gland increased on the 1st, 12th and 24th week (P < 0.05).</p><p><b>CONCLUSIONS</b>After parasympathectomy of rat submandibular glands, the saliva flow rate at rest increased in the denervated gland, which suggests that parasympathectomy of submandibular gland might be used as a therapy for xerostomia.</p>

High glucose increases periostin expression and the related signal pathway in adult rat cardiac fibroblasts / 生理学报

Cardiac fibrosis is a major mechanism contributing to myocardial systolic and diastolic dysfunction in diabetic cardiomyopathy. Periostin is a novel extracellular matrix protein, secreted from cardiac fibroblasts, and closely related with cardiac fibrosis and remodeling. The present study aimed to investigate the effect of high glucose on periostin expression and the related signal transduction pathway in cardiac fibroblasts. Adult rat cardiac fibroblasts were cultured and stimulated with high glucose (25 mmol/L). The mRNA and protein expressions of periostin were detected by RT-PCR and Western blot, respectively. Intracellular reactive oxygen species (ROS) production was measured using 2, 7-dichlorofluorescein diacetate (DCF-DA), an oxidant-sensitive fluorescent probe. Results showed that the mRNA expression of periostin in adult rat cardiac fibroblasts was increased by 117.26% when treated with high glucose for 12 h. Incubation with high glucose for 24 h enhanced periostin protein expression by up to 93.12%. High glucose induced the production of ROS in adult rat cardiac fibroblasts, which was reduced by chelerythrine (CLT), a protein kinase C (PKC) inhibitor. High glucose-induced periostin protein expression was decreased significantly when pretreated with CLT or N-acetylcysteine (NAC), a ROS scavenger. The phosphorylation of c-jun N-terminal protein kinase (JNK) was increased markedly when stimulated with high glucose for 30 and 60 min, which was abolished when pretreated with CLT or NAC. SP600125, a specific JNK inhibitor, significantly decreased periostin expression induced by high glucose. In conclusion, high glucose stimulates periostin protein expression via a PKC/ROS/JNK-dependent pathway in adult rat cardiac fibroblasts.

Effect of botulinum toxin-A on secretion of parasympathetic denervated rabbit submandibular gland / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of botulinum toxin-A (BTX-A) on secretion of parasympathetic denervated rabbit submandibular gland.</p><p><b>METHODS</b>Twenty-four rabbits were divided into 3 groups: control (n = 4), parasympathetic denervated submandibular gland (n = 4), and parasympathetic denervated submandibular gland with 5 U BTX-A injection (n = 16). Secretion flow was measured by Schirmer test. Composition of saliva was detected by biochemical method.</p><p><b>RESULTS</b>Secretion of parasympathetic denervated submandibular gland increased by 139.0% in rest time (P < 0.01), but decreased by 64.2% in feeding time (P < 0.01) compared with controls. Secretion of submandibular gland decreased in rest time 1, 2, 4, and 12 weeks after BTX-A injection compared with that of parasympathetic denervated submandibular gland without injection (P < 0.05), which was also the same in feeding time 1 and 2 week after injection (P < 0.05). The concentrations of amylase, sodium, potassium, chloride and protein of saliva were not changed after BTX-A injection.</p><p><b>CONCLUSIONS</b>BTX-A could decrease the secretion of parasympathetic denervated submandibular gland.</p>

Crosstalk between angiotensin II and platelet derived growth factor-BB mediated signal pathways in cardiomyocytes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Angiotensin II (AngII) and platelet-derived growth factor (PDGF)-BB can induce hypertrophy in the cultured rat cardiomyocytes through different signal transduction pathways. AngII stimulates growth through G protein coupled receptor (GPCR), while PDGF-BB acts via receptor tyrosine kinase (RTK). Although there has been much development on the individual AngII and PDGF-BB mediated signal pathways, little is known about the interactions between these two factors. Therefore, the crosstalk between AngII and PDGF-BB mediated signal pathways in the rat cardiomyocytes was investigated in this study.</p><p><b>METHODS</b>Primary culture of neonatal rat ventricular myocytes was prepared. The amount of tyrosine-phosphorylated and non-phosphorylated PDGF-beta receptor, G(alphaq/11), and phospholipase C (PLC) beta(3) were measured by immunoblotting analysis. The statistical analysis was done by one-way ANOVA.</p><p><b>RESULTS</b>Tyrosine-phosphorylated PDGF-beta receptor was increased by 120.60% at 1 minute and recovered to the control level at 10 minutes after AngII stimulation. Phosphorylation of PDGF-beta receptor triggered by AngII was blocked by losartan, a specific antagonist of AT1 receptor. PLC inhibitor U73122, protein kinase C (PKC) inhibitor staurosporine (STS) and mitogen-activated ERK activating kinase (MEK) inhibitor PD98059 also inhibited the AngII-induced phosphorylation of PDGF-beta receptor. PDGF-BB slightly increased the expression of G(alphaq/11) protein.</p><p><b>CONCLUSION</b>AngII transactivates PDGF-beta receptor via AT(1) receptor-G(alphaq/11)-PLC-PKC pathway in the rat cardiomyocytes. ERK also participates in the transactivation of PDGF-beta receptor triggered by AngII.</p>

Effect of AMP-activated protein kinase on cardiovascular protection of adiponectin / 生理学报

Adiponectin, derived mainly from white adipose tissue, regulates glucose and fatty acid metabolism and has anti-inflammatory and anti-atherosclerotic properties. The decrease in plasma adiponectin concentration contributes to the development of metabolic and cardiovascular diseases. AMP-activated protein kinase (AMPK) is a serine/threonine kinase which plays an important role in regulating many cellular processes, particularly pathways involved in cellular energy status. AMPK is now recognized as a fuel gauge in mammalian cells. Adiponectin activates AMPK phosphorylation and then promotes ATP-generating pathways in heart, including glucose transport, glycolysis, and fatty acid oxidation. The recent evidence has shown that AMPK activation has an important role in the vasculature where it may exert anti-atherosclerotic effects. Phosphorylation of AMPK induced by adiponectin inhibits protein synthesis, and may be an adaptive response to pathological cardiac hypertrophy. AMPK also has a cardioprotective role against myocardial injury and apoptosis in the ischemic heart. This review will discuss the role of AMPK in adiponectin-mediated protective properties of cardiovascular diseases.

Expression of alpha1-adrenoceptor and promoting secretory response by phenylephrine in rabbit submandibular gland / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the expression and distribution of alpha1-adrenoceptor subtypes in rabbit submandibular gland and the effect of phenylephrine on salivary secretion.</p><p><b>METHODS</b>The expressions of alpha1A-, alpha1B-, and alpha1D-adrenoceptor mRNA and protein were investigated by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot in rabbit submandibular gland. Immunohistochemical assay was applied to detect the distribution of alpha1A-, alpha1B-, and alpha1D-adrenoceptor and localization of aquaporin 5 in rabbit submandibular gland. Different concentrations of phenylephrine (1 x 10(-8))-(1 x 10(-6)) mol/L were administrated through a polyethylene tube, which was intubated into Wharton's duct of submandibular gland. Heart rate and blood pressure of rabbits were observed during phenylephrine administration. Salivary flow was measured by the length of moist filter paper (35 mm x 5 mm) within 5 min.</p><p><b>RESULTS</b>Alpha1A-, alpha1B-, and alpha1D-adrenoceptor mRNA and protein were expressed in rabbit submandibular gland. Three alpha1-adrenoceptor subtypes were widely distributed in the membrane and cytoplasma of both acinar and ductal cells. Phenylephrine (1 x 10(-7) mol/L, 100 microl) stimulated effectively salivary secretion without inducing significant alteration of blood pressure and heart rate in rabbit. Immunohistochemical assay showed that aquaporin 5 was mainly localized in the apical and lateral plasma membrane in both acinar and ductal cells in unstimulated condition, while the expression of aquaporin 5 was increased after administration of phenylephrine.</p><p><b>CONCLUSIONS</b>Expression of alpha1A-, alpha1B-, and alpha1D-adrenoceptor mRNA and protein was existed in rabbit submandibular gland. Phenylephrine safely and effectively promoted salivary secretion when it was administrated through Wharton's duct of submandibular gland. The mechanism of phenylephrine on salivary secretion may involve in the increase of expression of aquaporin 5 in the apical and lateral plasma membrane in rabbit submandibular gland. This study will hopefully lead to a novel strategy for clinical treatment of dysfunction of submandibular gland.</p>

Expression of COX-2 and the relationship between COX-2 and PTEN in endometrial adenocarcinoma / 肿瘤研究与临床

Objective To study the expression and clinical significance of COX-2 and the relation- ship between COX-2 and PTEN in endometrial adenocarcinoma(EAC).Methods The expression of COX-2, PTEN protein was detected by SP-immunohistochemical method in EAC,endometrial intraepithelial neoplasia, corresponding normal endometrium.Results The positive rates of COX-2 protein increased from normal en- dometrium(13.33%) to endometrial intraepithelial neoplasia(50.00%) and adenocarcinoma(64.58 %)(P

Effect of Ang II on PDGF receptor expression in vascular smooth muscle cell / 中国应用生理学杂志

<p><b>AIM</b>To study the effect of angiotensin II (Ang II) on platelet-derived growth factor(PDGF) receptor expression in vascular smooth muscle cell(VSMC).</p><p><b>METHODS</b>Restenosis model was established by balloon injury in rat aorta. The morphologic change and level of Ang II were measured at 14th day after operation. The expression of PDGF-beta receptor was detected by Western blot. The cultured VSMC pretreated with or without losartan were treated with Ang II.</p><p><b>RESULTS</b>Compared with sham group, the sections of injured aorta showed marked intimal thickening with large numbers of VSMCs proliferation throughout intima and media, the level of Ang II obviously increased by 78.8% (P < 0.05), the expression of PDGF-beta receptor significantly increased by 83.9% (P < 0.05) at 14th day after operation. The expression of PDGF-beta receptor in cultured VSMC treated with Ang II was higher than that of control group (P < 0.01). The effect of Ang II was inhibited remarkably by pretreatment with losartan.</p><p><b>CONCLUSION</b>Ang II can stimulate PDGF receptor expression in VSMC, it may be an important mechanism of Ang II-induced VSMC proliferation.</p>

Angiotensin II induced upregulation of G alpha q/11, phospholipase C beta 3 and extracellular signal-regulated kinase 1/2 via angiotensin II type 1 receptor / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The role of the G alpha q/11-mediated signal transduction pathway in angiotensin II (AngII) induced cardiac hypertrophy remains unclear. This study was to investigate the role of the G alpha q/11 signal transduction pathway in the development of cardiac hypertrophy in 2K1C hypertensive rats and in cultured neonatal rat ventricular myocytes (NRVMs) and to elucidate the effects of the pathway on AngII induced cardiac hypertrophy.</p><p><b>METHODS</b>Renal hypertension was induced in 2K1C hypertensive rats by placing a silver clip around the left renal artery. At 8 weeks after operation, the systolic blood pressure, the ratio of left ventricular weight to body weight (LV/BW), and the concentration of AngII in the heart were measured. The protein levels of G alpha q/11 and extracellular signal-regulated kinase 1/2 (ERK1/2) were assayed by Western blot analysis, and the activity of phospholipase C (PLC) in the myocardium was detected using [(3)H]-PIP2 as a substrate. Changes in [(3)H]-leucine incorporation and in the protein levels of the signal molecules G alpha q/11, PLC beta 3, and ERK1/2 were measured after NRVMs were stimulated with 10(-7) mol/L AngII.</p><p><b>RESULTS</b>The protein levels of G alpha q/11 and ERK1/2 in the hearts of 2K1C rats increased by 35.8% and 31.9%, respectively, compared with the sham group. The PLC activity in the 2K1C group was also significantly increased (P < 0.05). The levels of G alpha q/11, PLC beta 3, and ERK1/2 increased significantly after NRVMs were stimulated by AngII. The upregulation of G alpha q/11, PLC beta 3 and ERK1/2 in NRVMs occurred prior to [(3)H]-leucine incorporation increases, and could be inhibited with losartan.</p><p><b>CONCLUSION</b>AngII can initiate cardiac hypertrophy and upregulate signal molecules in the G alpha q/11-mediated signal transduction pathway, such as G alpha q/11, PLC beta 3 and ERK1/2, at both tissue and cellular levels.</p>

Role of platelet-derived growth factor receptor-mediated signal transduction in myocardial hypertrophy of spontaneously hypertensive rats / 生理学报

The role of platelet-derived growth factor (PDGF) receptor-mediated signal transduction in myocardial hypertrophy of spontaneously hypertensive rats (SHR) was investigated. The protein expressions of PDGF beta receptor and extracellular signal-regulated kinase 1/2 (ERK 1/2) and the level of phosphorylated ERK 1/2 (pERK 1/2) in cardiac tissues from 4- and 12-week-old SHR and their age-matched normotensive control Wistar-Kyoto rats (WKY) were examined by Western blot analysis. The results showed that arterial systolic and diastolic blood pressure, +/-dp/dt(max) and the ratio of left ventricular weight to body weight were unchanged in 4-week-old SHR, while they were increased significantly in 12-week-old SHR as compared with those of age-matched WKY. There were no differences in PDGF beta receptor, pERK 1/2, and ERK 1/2 between 4-week-old WKY and SHR. The expression of PDGF beta receptor of 12-week-old SHR was significantly increased by 32.77% (P<0.05) as compared with that of age-matched WKY. Although the expression of ERK 1/2, the downstream signal molecule of PDGF receptor-mediated signal transduction pathway, was unchanged, the level of pERK 1/2, the active form of ERK 1/2, was increased by 19.6% (P=0.01) in 12-week-old SHR. To further elucidate the effect of PDGF beta receptor on cardiomyocyte growth and the relation between PDGF beta receptor and ERK 1/2 activity, (3)H leucine incorporation assay and immunoblotting analysis of pERK 1/2 were performed after cultured neonatal rat cardiomyocytes were stimulated with PDGF-BB. It was shown that (3)H leucine incorporation and pERK 1/2 level were significantly increased after PDGF-BB stimulation. These findings suggest that PDGF beta receptor may play an important role in the myocardial hypertrophy of spontaneously hypertensive rats.