Evidence for functional,inhibitory, histamine H3 receptors in rat carotid body Type I cells

The Type I cells are the sensory elements of the carotid bodies and play a critical role in defining the ventilatory response to hypoxia and hypercapnia. Type I cells release multiple neurotransmitters during a chemosensory stimulus resulting in increased firing of the carotid sinus nerve and modification of the breathing pattern. While much is known about the actions of individual neurotransmitters in this system, very little is known about how multiple neurotransmitters may integrate to shape the output of the carotid body. Recent data has indicated that the neurotransmitter histamine does not excite isolated Type I cells despite being released during hypoxia and its receptors being present on the Type I cells. Here the hypothesis that histamine might modulate an excitatory neurotransmitter such as acetylcholine was tested. Using calcium imaging techniques it was found that histamine attenuated calcium signaling events initiated by the muscarinic acetylcholine receptor agonist acetyl-β-methylcholine via an H3 receptor mediated mechanism. In summary, these results suggest that when acetylcholine and histamine are co-released from Type I cells in response to chemostimuli, histamine may attenuate or modulate the excitatory presynaptic actions of acetylcholine.     

Striatonigral GABA,dynorphin, substance P and neurokinin A modulation of nigrostriatal dopamine release: evidence for direct regulatory mechanisms

Summary The striatonigral pathway contains several neurotransmitters which may regulate the activity of the nigrostriatal dopamine projection in the rat. This was investigated by measuring extracellular dopamine levels in the striatum, using microdialysis, after injections of GABA (300 nmol/0.2 l), dynorphin A (0.5 nmol/0.2 l), substance P (0.07 mnol/0.2 l) or neurokinin A (0.09 nmol/0.2 l) into the ipsilateral substantia nigra, pars reticulata (SNR). Intranigral injections of GABA or dynorphin A inhibited, while intranigral injections of substance P or neurokinin A stimulated dopamine levels in the ipsilateral striatum. In rats with ibotenic acid lesions (2.5 g/0.5 l) in the SNR, intranigral injections of GABA or dynorphin A inhibited, while intranigral injections of substance P or neurokinin A stimulated dopamine levels in the ipsilateral striatum. These responses were not significantly different than those in unlesioned rats. Analysis of the intranigral lesion with in situ hybridization revealed a heavy loss of glutamic acid decarboxylase mRNA expression in the SNR and a significant loss of tyrosine hydroxylase (TH) mRNA expression in the SNC. Immunohistochemical analysis revealed a disappearance of TH-Like immunoreactivity (LI) im dendrites in the SNR, a considerable loss of TH-LI cell bodies in the SNC and a restricted loss of neuropeptide K-LI in the SNR around the tip of the injection cannula. Furthermore, lesioned rats rotated ipsilateral to the lesion after apomorphine (1 mg/kg, s.c.), indicating that the basal ganglia output mediated via the SNR GABA neurons was impaired on the lesioned side. Analysis of the striatum revealed that a dense TH-LI fiber network could still be seen on the lesioned side. Furthermore, basal and amphetamine stimulated extracellular dopamine levels in the striatum on the lesioned side were not significantly depleted. This indicates that the ascending nigrostriatal dopamine projection was functionally intact on the lesioned side. These findings indicate that intranigral GABA, dynorphin A, substance P and neurokinin A modulation of ipsilateral striatal dopamine release is mediated via direct action on the nigrostriatal projection. Thus, it is suggested that the striatonigral pathway, which contains GABA, dynorphin, substance P and neurokinin A, exerts a direct regulatory effect on the activity of the nigrostriatal dopamine projection.     

Neurotensin and substance P immunoreactive nerve endings in the guinea pig carotid sinus and their ultrastructural counterparts

Summary The carotid sinus of the guinea pig was analysed immunohistochemically for the occurrence of neuropeptides. Immunoreactivity (IR) for neurotensin (NT) and substance P (SP) is distributed in two different populations of nerve endings and varicosities. NT-IR fibers penetrate deeply into the tunica media of the elastic segment of the carotid sinus and form the large, branched lanceolate nerve terminals. Electron-microscopic investigations have revealed that the NT-IR varicosities correspond to the large afferent baroreceptor endings containing abundant mitochondria. SP-IR fibers are located mainly at the mediaadventitial border. They seem to be correlated to dense-core, vesiclecontaining varicosities identified in the electron microscope. Therefore, these fibers may constitute afferent and efferent perivascular plexus regulating the vascular tone of the carotid sinus wall.This paper is dedicated to Prof. Dr. R. Ortmann on the occasion of his 70th birthday     

Involvement of tachykinin receptors in oedema formation and plasma extravasation induced by substance P,neurokinin A,and neurokinin B in mouse ear

The involvement of tachykinin receptors in skin inflammation induced by substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) was investigated in mouse ears. Intradermal injection of tachykinins (0.1–100 pmol/site) into the ear skin produced oedema formation. RP 67580 (ED₅₀:0.34 mg/kg, i.v.) and SR 140333 (ED₅₀:0.19 mg/kg, i.v.), the non-peptide NK₁ receptor antagonists, inhibited SP-induced oedema. SR 140333 was also effective in preventing NKA- and NKB-induced oedema. SR 48968 (1 mg/kg, i.v.), a non-peptide NK₂ antagonist, induced a significant inhibition of NKA-induced oedema but had no effect on the response to SP and NKB. SR 142801 (3 mg/kg, i.v.), a non-peptide NK₃ antagonist, prevented only NKB-induced oedema. In contrast, phosphoramidon (0.1 and 0.5 mg/kg, i.v.), an endopeptidase inhibitor, enhanced the oedema response to tachykinins. SR 140333, SR 48968, and SR 142801 blocked the enhancement by phosphoramidon of the response to SP, NKA, and NKB, respectively. Plasma extravasation in ear skin was induced by i.v. injection of tachykinins (0.7–17.6 nmol/kg). RP 67580 (ED₅₀:0.15 mg/kg, i.v. for SP) and SR 140333 (ED₅₀:14.3 g/kg, i.v. for SP) inhibited tachykinin-induced plasma extravasation in ear skin. However, SR 48968 and SR 140281 had no effect on the vascular response to tachykinins. Chlorpheniramine (4 mg/kg, i.v.), a histamine H₁ blocker, inhibited the response to local SP but not to i.v. SP. These results suggest that in addition to the NK₁ receptors, functional NK₂ and NK₃ receptors may participate in the oedema response to local NKA and NKB in the ear skin. However, it appears that NK₁ receptors on blood vessels are involved predominantly in plasma extravasation induced by i.v. tachykinins in the ear.accepted by G. Letts     

Supersensitivity to substance P and physalaemin in rat salivary glands after denervation or decentralization

Substance P, a putative neurotransmitter in mammals, and physalaemin, present in the skin of an amphibian, are both undecapeptides and belong to the family of tachykinins. The secretory effect of these tachykinins on parotid and submaxillary glands of the rat was examined. Dose-response curves showed that in the unoperated glands maximal secretory responses were obtained to an intravenous dose of 5–10μg/kg of the tachykinins, that the amount of saliva secreted from the submaxillary gland was twice that from the parotid gland, and that physalaemin was more potent than substance P. Parasympathetic denervation of the parotid gland and decentralization of the submaxillary gland caused a marked sensitization to the tachykinins, as judged by lowered threshold doses for secretion and increased secretory responses to a series of submaximal doses 3 weeks postoperatively. Sensitization was less marked after sympathetic denervation and decentralization; in the parotid gland decentralization caused, in fact, no sensitization while in the submaxillary gland the degree of sensitization was about the same after the two types of operation. The tachykinins acted directly on the gland cells and the effect was not exerted via cholinergic, α-adrenergic or β-adrenergic receptors. The pattern of sensitization to the tachykinins, found in the present study, after the different types of operation is similar to that previously found to cholinergic and α-adrenergic agonists and different from that to a β-adrenergic agonist. Studies by others have shown that in the rat parotid gland peptidergic receptors share a common intracellular pathway with cholinergic and α-adrenergic receptors, whereas β-adrenergic receptors use another pathway. In the present study it is suggested that this intracellular arrangement is of importance for the development of supersensitivity.     

Immunohistochemical localization of substance P and substance P receptor (NK1) in the olivary pretectal nucleus of the rat

The olivary pretectal nucleus (OPN) is the first central nucleus in the pupillary light reflex arc (PLR). Substance P (SP) is a neuropeptide present in the OPN. The present immunohistochemical study, performed at the ultrastructural level, aimed to determine the synaptic localization of SP and SP receptor in the OPN. Three types of SP-positive terminals were found. The most abundant type was of retinal origin, characterized by electron-lucent mitochondria and round vesicles, organized in glomerular structures, making asymmetric synaptic contacts with dendrites, and profiles containing pleomorphic vesicles, also making synaptic contacts with dendrites. The second type of SP-immunoreactive terminal contained electron-dense mitochondria and pleomorphic vesicles. This type made symmetric synaptic contacts and may originate from the ventral part of the lateral geniculate nucleus. The third type of SP-immunoreactive terminals contained electron-dense mitochondria, clear round vesicles, and made an asymmetric synaptic contact. This type originates from the contralateral OPN. SP receptors of the NK1 subtype were revealed to be on dendrites and were part of the glomerular-like arrangement. On account of the present observations, it can be concluded that retinal projections to the OPN use SP as a neuromodulator and synapse on NK1 receptor-containing dendrites of large neurons projecting to the Edinger-Westphal nucleus. Since SP also modulates the parasympathetic component of the PLR, we postulate that SP plays a modulating role in all components of the PLR.     

Distribution of carotid body type I cells and other periadventitial type I cells in the carotid bifurcation regions of the cat

Summary The bilateral distribution of carotid body type I cells was investigated in five non-pedigree cats by serially sectioning the carotid bifurcation regions. Carotid body type I cells occurred bilaterally in close proximity to the wall of the occipital artery or one of its proximal branches, and less frequently the ascending pharyngeal artery within a division of connective tissue with defineable but irregular borders. Caudally, and separate from the principal mass of carotid body type I cells, isolated groups of periadventitial type I cells were found in seven out of ten specimens lying freely in the connective tissues around the occipito-ascending pharyngeal trunk and the origin of the occipital artery immediately rostral to the carotid bifurcation. Periadventitial type I cells were not observed at the level of the carotid bifurcation but on one occasion these cells were noted caudal to the carotid bifurcation lying adjacent to the wall of the rostral end of the common carotid artery. From our data on four specimens, reconstructions were made of the carotid body. The occurrence and significance of the periadventitial type I cells is discussed.     

Place aversion induced by the substance P analogue,dimethyl-C7, is not state dependent: implication of substance P in aversion

Summary Intraventricular infusion of the stable substance P analogue, DiMethyl-C7, was found to produce aversion in a place conditioning paradigm. This effect was independent of state dependent learning since the place aversion was also seen when the subjects were tested under the influence of the drug. A role for substance P in aversion is discussed.     

The volume of the carotid body and periadventitial type I and type II cells in the carotid bifurcation region of the fetal cat and kitten

Summary The bilateral distribution of carotid body type I cells was investigated in 6 fetuses (gestational age 95%) and 9 newborn kittens (aged 1 day to 4 days) by serially sectioning the carotid bifurcation regions. In most specimens type I cells occurred in close proximity to the wall of the occipital artery or one of its small proximal branches within a division of connective tissue with defineable but irregular borders. This combination of type I cells and connective tissue constituted the principal mass of the carotid body. Using an interacting image analysis system, the area of the carotid body in each serial section was measured by accurately contouring its perimeter. The volume of the carotid body was calculated by multiplying the sum of the areas of the serial sections by the thickness of the section. The volume of the carotid body was 0.052±0.018 mm³ in the fetuses and 0.025–0.117 mm³ in the 1–4 day old kittens. A degree of symmetry in the values for the volume of the right and left carotid body was found. Caudally, and separate from the principal mass of carotid body type I cells, isolated groups of periadventitial type I cells were noted in the connective tissues around the occipito-ascending pharyngeal trunk, origin of the occipital artery and rostral end of the common carotid artery in 7 out of 12 specimens from fetal cats and 11 out of 18 specimens in newborn kittens. The volumes of the periadventitial groups of cells ranged between 25–1,365 m³ in fetuses and 10–1,351 m³ in kittens.     

Measurements of potassium changes in the cat carotid body under hypoxia and hypercapnia

With the aid of potassium-sensitive microclectrodes reinforced by bitumen (tip diameter, 1.5 m), extracellular potassium activity ([K⁺]_e) and DC potential were measured in the cat's carotid body. Under normoxic and normocapnic conditions, potassium values of 1–16 mM (mean value 7.2 mM, standard deviation 3.8 mM) and DC potential values of –11 mV to +13 mV were recorded. With hypoxia, [K⁺]_e increased by between 1 mM and 9 mM; DC potential was reduced by between 0.5 and 3 mV. With hypercapnia, [K⁺]_e decreased by between 1 mM and 5 mM: changes in DC potential were variable. The results suggest that, during hypoxia, potassium influences the nervous structures in the carotid body whereas this influence is absent during hypercapnia.     

A theoretical analysis of the carotid body chemoreceptor response to O2 and CO2 pressure changes

A simple mathematical model of the carotid body chemoreceptor response is presented. The model assumes that the static chemoreceptor characteristic depends on oxygen saturation in the arterial blood and on CO2 arterial concentration. The values of O2 saturation and of CO2 concentration are computed, from pressure, using blood dissociation curves, which include both the Bohr and Haldane effects. Moreover, the O2-CO2 static responses interact via a multiplicative term followed by an upper saturation. The dynamic response includes a term depending on the time derivative of CO2 concentration and a low-pass filter, which accounts for the time required to reach the steady state level. With a suitable choice of its parameters, the model reproduces the carotid chemoreceptor response under a variety of combined O2 and CO2 stimuli, both in steady state conditions and in the transient period following acute CO2 or O2 pressure changes. In particular, simulations show that if two hypercapnic stimuli are given in rapid succession, the response to the second stimulus is weaker than the first. Moreover, during transient conditions the effect of CO2 pressure changes prevail over the effect of O2 changes, due to the intrinsic derivative component of the response to CO2. In conclusion, the model allows present knowledge about chemoreceptor activity to be summarized in a single theoretical framework. In perspective, it may be used as an afferent block within large-scale models of the overall cardio-respiratory control system.     

New insight into the role of substance P/neurokinin-1 receptor system in breast cancer progression and its crosstalk with microRNAs

The neuropeptide substance P (SP) triggers a variety of tumor-promoting signaling pathways through the activation of neurokinin-1receptor (NK1R), a class of neurokinin G protein-coupled receptors superfamily. Recent researches in our and other laboratories have shown the overexpression of both SP and NK1R in breast cancer (BC) patients. SP/NK1R signaling is strongly implicated in the pathogenesis of BC through affecting cell proliferation, migration, metastasis, angiogenesis, and resistance. Therefore, SP/NK1R signaling responses must be rigorously regulated; otherwise, they would contribute to a more aggressive BC phenotype. Recently, microRNAs (miRNAs) as a specific class of epigenetic regulators have been shown to regulate NK1R and thus, controlling SP/NK1R signaling responses in BC. This review summarizes the current knowledge of the role of SP/NK1R signaling and its therapeutic potentials in BC. We also provide an overview regarding the effects of miRNA-mediated NK1R regulatory mechanisms in controlling BC tumorigenesis to gain a clearer view and thus better management of cancer.     

Respiratory responses to intermittent hypoxia in unsedated piglets: relation to substance P binding in brainstem

Respiratory responses to single intermittent hypoxia (5 min 21% O(2), 5 min 8% O(2) X6) in 5-6, 10-11, 21-22 and 26-27 day-old piglets, and to recurrent six daily intermittent hypoxia in 10-11 and 26-27 day-old piglets were assessed. Substance P binding in the piglets' brainstem immediately after the last hypoxic episode was measured. All piglets hyperventilated during hypoxia. Weight adjusted inspired ventilation, tidal volume and instantaneous flow decreased with age. The oldest piglets uniquely displayed attenuated ventilation and tidal volume during the sixth versus first hypoxic episode with single intermittent hypoxia, and reduced inspired ventilation and tidal volume during the first hypoxic episode on the sixth daily hypoxia compared to single hypoxia. By contrast, substance P binding was greatly reduced in the solitary, hypoglossal, paraambigual and lateral reticular brainstem nuclei of both younger and older piglets following either single or recurrent intermittent hypoxia. Thus, the reduction in membrane-bound neurokinin receptors by intermittent hypoxia, presumably consequent to endogenously released substance P, does not exclusively determine whether the ventilatory response to that hypoxia will be attenuated or not.     

Up-regulation of substance P binding sites in the vagus nerve projection area of the cat brainstem after nodosectomy. A quantitative autoradiographic study

Substance P (SP) regulates visceral functions in the nucleus of the solitary tract (NST) area. High affinity SP binding sites labelled with [³H]SP or [¹²⁵I]SP show a heterogeneous distribution in the cat medulla with high densities in the rostral and dorso-caudal parts of both the median subnucleus of NST and the dorsal motor nucleus (DMN). We previously observed a significant loss of SP immunoreactivity in the vagal area of the cat after an ipsilateral nodosectomy. It was thus important to study the correlated plasticity of SP binding in the context of the regulation of receptor function. Whichever labelled ligand was used, a unilateral nodose excision was followed by an ipsilateral increase in SP binding in the NST (200%) and the DMN (300%) after 30 days of survival. This increase was region-specific and did not match exactly the decrease in SP immunoreactivity following nodosectomy. This SP receptor density up-regulation could be due to long-term deprivation of SP afferent fibres in the NST and partly in the DMN. In the latter the increase of SP receptors occurred in both the cytoplasm of large neurons and the neuropile and did not affect the glia. The up-regulation phenomenon seems to be specific for SP receptors in the cat (at least in the DMN) and may constitute a reactive mechanism against the injury of axotomy of DMN neurons.     

Expression of HIF-1alpha, VEGF and VEGF receptors in the carotid body of chronically hypoxic rat

We examined the protein expression and localization of HIF-1alpha, VEGF, VEGF receptors in the carotid body (CB) of rats breathing 10% inspired oxygen for up to 4 weeks. The immunoreactivity (IR) of HIF-1alpha was distributed numerously in the nuclei of glomus (type-I) and other cells since hypoxia for 1 day, but was faint and scattered in the normoxic CBs. Cytoplasmic staining of the VEGF was intense in glomus cells of the hypoxic but not the normoxic group. The IR levels of HIF-1alpha and VEGF reached plateau at 4 weeks, and the IRs of VEGFR-1 and VEGFR-2 were strongly positive in the hypoxic group. Yet, the expression of VEGFR-1-IR was mild, whereas the VEGFR-2-IR was intense in normoxic CBs, suggesting an upregulation of VEGFR-1 but not VEGFR-2 in hypoxia. Hence, HIF-1 may activate the expression of VEGF and VEGFR-1 in the CB and the expression of VEGF in the chemoreceptors may play a paracrine role in the vascular remodeling during chronic hypoxia.     

内皮素-1介导循环间歇性低氧影响大鼠颈动脉体可塑性的机制

目的 探讨内皮素-1（ET-1）介导循环间歇性低氧（CIH）影响颈动脉体可塑性的潜在分子机制。 方法（1）动物实验：将32只雄性SD大鼠随机分为2组,常氧对照组（Con）和循环间歇性低氧模型组（CIH）,每组16只。模型制作21d后,将每组（Con和CIH）16只大鼠再分为2组,分别予尾静脉注射ET-1（1×10^-6 mol/kg体重）或按照上述剂量计算的等体积生理盐水。30 min后,收集颈动脉体,采用Western blotting检测相关信号通路分子蛋白水平的变化。（2）器官培养：离体培养颈动脉体组织,ET-1（1×10^-4 mol /L）处理不同时间（0 min、10 min、60 min）,通过Western blotting检测p38丝裂原活化蛋白激酶（p38 MAPK）磷酸化水平。 结果 （1）CIH上调颈动脉体内皮素受体A（ET-A）和ET-B蛋白的表达;（2）与其他各组相比,ET-1可显著上调CIH大鼠颈动脉体磷酸化蛋白激酶A（p-PKA）、p-p38 MAPK、磷酸化的钙调蛋白激酶Ⅱ（p-CaMKⅡ）、磷酸化的环磷腺苷效应元件结合蛋白 （p-CREB）磷酸化水平和RhoA蛋白表达水平;（3）ET-1上调离体器官培养的颈动脉体p-p38 MAPK磷酸化水平,10 min较60 min明显。 结论 ET-1可能通过PKA/p38 MAPK/CaMKⅡ/CREB和RhoA信号通路调控CIH诱导的颈动脉体可塑性。     

Colocalization of neuronal nitric oxide synthase and neurokinin-1 receptor in striatal interneurons in the rat

It has been established that nitric oxide synthase (NOS)-containing aspiny neurons constitute one class of interneurons in the striatum, and that substance P (SP)-containing projection neurons give off many axon collaterals within the striatum. In the present study, we investigated a morphological substrate of possible influences of SP-containing projection neurons upon NOS-containing interneuron in the rat striatum; colocalization of immunoreactivities for NOS and NK-1 type tachykinin receptor (NK1R: SP receptor) was examined by a double-immunofluorescence histochemistry. The vast majority (94.6%) of NOS-positive neurons showed NK1R immunoreactivity, whereas only smaller cells of NK1R-positive neurons (61.2% of NK1R-positive neurons) displayed NOS immunoreactivity. The results indicated that the NOS-containing interneurons were under direct control of SP-containing projection neurons in the striatum.     

Plasma and synovial fluid interleukin-1, interleukin-6 and substance P concentrations in rheumatoid arthritis patients: Effect of the nonsteroidal anti inflammatory drugs indomethacin,diclofenac and naproxen

We performed an open, between patients, placebo controlled study in order to evaluate the effect of the treatment with the non steroidal anti inflammatory drugs indomethacin, diclofenac and naproxen on the concentrations of the cytokines IL-1 and IL-6 and of the neuropeptide substance P in plasma and synovial fluid of 24 rheumatoid arthritis patients. All patients had high synovial fluid cytokine and substance P levels, and high plasma cytokine levels at the beginning of the study. The treatment with the non steroidal anti inflammatory drugs significantly decreased both plasma and synovial fluid IL-6 and synovial fluid substance P in comparison to placebo, but did not affect IL-1 concentrations. This effect can participate in the therapeutic effect of non steroidal anti inflammatory drugs in rheumatoid arthritis.     

Responses of functionally identified neurones in the dorsal horn of the cat spinal cord to substance P, neurokinin A and physalaemin.

The mammalian tachykinins, substance P and neurokinin A, and the non-mammalian tachykinin, physalaemin, were tested on functionally identified dorsal horn neurones in vivo. The experiments were done on cats which were anaesthetized with sodium pentobarbital or were anaemically decerebrated. Extracellular single-unit recordings were made in the lumbar spinal cord and the tachykinins were applied by iontophoresis. Each neurone was classified functionally as wide dynamic range, non-nociceptive, nociceptive specific or proprioceptive. The response to tachykinin application was determined for each neurone. Application of each of the tachykinins evoked a characteristic excitatory response which was delayed in onset, slow in developing and prolonged: physalaemin excited 99/131 neurones tested, neurokinin A excited 45/63 neurones and substance P excited 32/49 neurones. With two neurones physalaemin evoked a depression of the rate of firing, which may have been caused indirectly by excitation of a neighbouring neurone. Such depression was not elicited by either substance P or by neurokinin A. Physalaemin had a preferential excitatory effect on nociceptive neurones evoking excitation of 76/94 nociceptive neurones compared with 12/23 non-nociceptive neurones (chi 2 = 7.9, 1 d.f., P = 0.005). Substance P also caused a preferential excitation, with 30/40 nociceptive neurones being excited while all of the non-nociceptive neurones (n = 7) were unaffected (chi 2 = 11.5, 1 d.f., P = 0.0007). In contrast, neurokinin A failed to have a preferential effect; 32/46 nociceptive and 9/10 non-nociceptive neurones were excited (chi 2 = 1.0, 1 d.f., P = 0.40). Comparing the proportions of nociceptive neurones excited by the different tachykinins indicated that this type of neurone was not differently sensitive to any of the three peptides (chi 2 = 3.2, 2 d.f., P = 0.20). On the other hand, non-nociceptive neurones were preferentially excited by neurokinin A and physalaemin compared with substance P (chi 2 = 13.4, 2 d.f., P = 0.001). With regard to the endogenous tachykinins the results of this study may be interpreted in the following ways. The differential excitatory effect of substance P on nociceptive neurones supports the proposed role for this peptide in the transmission specifically of nociceptive inputs at the first afferent synapse. On the other hand, as neurokinin A excited non-nociceptive as well as nociceptive neurones, there may be a functional role for neurokinin A distinct from that of substance P.     

P物质对成纤维细胞Rac-1/JNK通路及糖尿病创面愈合的影响

目的 研究外源性P物质(SP)对成纤维细胞迁移的影响及糖尿病小鼠创面愈合的作用.方法 利用Transwell细胞迁移试验、划痕试验检测SP对小鼠成纤维细胞迁移能力的影响.筛选建模成功的糖尿病小鼠20只,随机分为对照组和SP组.分别于皮肤损伤后4、8、12、16、20d,观察创面愈合情况并计算创面愈合率,并于7、14、2...