Microinjection of endomorphin-1 in the ventrolateral periaqueductal gray induces descending inhibition of cardiac nociception by activating μ-opioid receptor in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe descending inhibition of cardiac nociception induced by microinjection of endomorphin-1 (EM1) in the ventrolateral periaqueductal gray (VLPAG) in rats effect and explore the role of μ-opioid receptor in mediating this effect.</p><p><b>METHODS</b>Male SD rats were randomized into electromyography (EMG) group and c-Fos group, both of which were further divided into 5 subgroups, namely 0.9% NaCl group, bradykinin (BK) group, BK+EM1 group, BK+CTOP group, and BK+CTOP+EM1 group. Rat models of cardiac nociception were established by intrapericardial injection of BK. The changes of cardiaosomatic motor reflex induced by BK were observed by assessing EMG responses of the dorsal spinotrapezius muscle; c-Fos expression in the spinal dorsal horn at levels T-T was tested.</p><p><b>RESULTS</b>Compared with 0.9% NaCl, intrapericardial BK injection induced obvious EMG activities and significantly increased c-Fos expression in the spinal dorsal horn at T-T ( < 0.05). Compared with BK injection, microinjection of EM1 in the VLPAG dose-dependently inhibited EMG activities and significantly decreased c-Fos expression ( < 0.05); microinjection of CTOP in the VLPAG produced no significant effect on EMG or c-Fos expression ( > 0.05). Microinjection of CTOP obviously reversed EM1-induced inhibition of EMG activities and c-Fos expression ( < 0.05).</p><p><b>CONCLUSIONS</b>Microinjection of EM1 in the VLPAG produces descending inhibition of cardiac nociception in rats by activating μ-opioid receptor.</p>

Comparison of curative effects between different minimally invasive methods in treatment of varicose veins in lower extremities / 吉林大学学报(医学版)

Objective:To compare the clinical effects of different minimally invasive surgeries in the treatment of varicose veins of lower extremities,and to explore their application values.Methods:A total of 201 patients with varicose veins of lower extremities were selected and treated with different operation methods.52 cases were treated by endovenous laser therapy(EVLA group),46 cases were treated by transilluminated powered phlebectomy (TIPP group),49 cases were treated by EVLA combined subfascial endoscopic perforator surgery(SEPS)(EVLA+SEPS group)and 54 cases were treated by TIPP combined SEPS(TIPP+SEPS)group.The operation time, the intraoperative blood loss,the postoperative hospitalization cost,the hospitalization time,the incidence rates of postoperative complications(residual varicose veins,subcutaneous induration,superficial phlebitis,skin necrosis and saphenous nerve injury)of the patients in various groups were compared.Results:There were significant differences in the operation time,the intraoperative blood loss and the postoperative hospitalization time,the hospitalization cost of the patients between various groups(P<0.05).Compared with EVLA group,the incidence rats of residual varicose veins,superficial phlebitis,and lower extremity swelling and ecchymosis of the patients in TIPP group were significantly decreased(P<0.05);the incidence rates of subcutaneous induration,wound hematoma,saphenous nerve injury and skin numbness were increased,but there were no significant differences (P>0.05).Compared with EVLA group and TIPP group,the incidence rates of reidual varicose veins and superficial phlebitis in EVLA + SEPS group and TIPP + SEPS group were significantly decreased(P<0.05). The healing rates of the patients 3 months after operation in TIPP group,EVLA+ SEPS group and TIPP+ SEPS group were significantly increased compared with EVLA group(P<0.05).The recurrence rates 1 year after operation in TIPP group,EVLA + SEPS group and TIPP + SEPS group were lower than that in EVLA group (P<0.05).Conclusion:The curative effects of EVLA combined with SEPS and TIPP combined with SEPS in treatment of varicose veins in lower extremities are superior to EVLA and TIPP,with the advantages of safe and reliable methods,complete varicose vein resection,less postoperative complications,quick ulcer healing and low recurrence rate and so on.

The modulation of central amygdale on cardiac nocicepption in rats / 西安交通大学学报(医学版)

Objective To study the modulation of central amygdale (CeA)on cardiac nociception with electrical stimulation in rats.Methods The heart pain model of adult male Sprague-Dawley rats was established with intrapericardial injection of capsaicin; then the evoked electromyography (EMG ) responses in the spinotrapezius (SPT)were observed as an index.Immunohistochemical method was used to observe the expression of c-fos in CeA;The rats were divided into normal control group,intrapericardial saline injection control group,and intrapericardial capsaicin injection group. The changes of EMG responses after electrical stimulation on CeA (intensity of 30μA and 70μA)were observed separately by electrophysiology in different groups.Results① Compared with normal control group, intrapericardial capsaicin injection group had significantly increased expression of c-fos in CeA.However,c-fos expression did not differ significantly between intrapericardial saline injection group and normal control group;② After 30μA electrical stimulation on CeA,EMG response in SPT significantly decreased in intrapericardial capsaicin injection group compared with that in control group;the total discharge rate was (78.58±4.62)% of that of control group (P<0.05).After 70μA electrical stimulation on CeA, the total discharge rate was (54.89±3.98)% of that of control group (P<0.05).Conclusion CeA may be involved in cardiac nociceptive transmission in rats and has inhibitory effects on the modulation of rat cardiac nociception.

Regulation of metabotropic glutamate subtype 7 and 8 receptors in nucleus tractus solitarius in cardiac nociception in rats / 吉林大学学报(医学版)

Objective To explore the role of metabotropic glutamate receptors (mGluRs)group Ⅲ and its subtypes mGluR7 and mGluR8 in nucleus tractus solitarius(NTS)in cardiac-somatic motor reflex (CMR),and to clarify the modulation role of mGluR Ⅲ and its subtypes in NTS in cardiac nociceptoion.Methods 40 SD rats were randomly divided into L-AP4 group,microinjection of mGluRs Ⅲ agonist L-AP4 0.1,1.0,10.0 or 20.0 nmol in NTS;AMN082 group,microinjection of mGluR7 agonist AMN082 1,2 or 4 nmol;DCPG group,microinjection of mGluR8 agonist DCPG 4, 6 or 8 nmol;MSOP group, microinjection of mGluR Ⅲ antagonist MSOP 20 or 100 nmol,20 nmol MSOP+410 nmol L-AP,20 nmol MSOP+2 nmol AMN082,20 nmol MSOP+6 nmol DCPG. The changes of CMR of the rats in various groups were observed.Results Compared with control,the CMR in L-AP4 and AMN082 groups was decreased (P0.05);the CMR in MSOP group after injection of 100 nmol MSOP was increased (P0.05).Conclusion The group Ⅲ mGluRs in the NTS play an inhibitory role in cardiac nociception, and mGluR7 has anti-nociceptive effects while mGluR8 has pro-nociceptive effects.

Modulatory effect of neurokinin-1 and non-N-methyl-D-aspartate receptors on cardiosomatic reflex in rat spinal cord / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the role of neurokinin-1 (NK1) receptor and non-N-methyl-D-aspartate (non-NMDA) receptor in modulating the cardiosomatic reflex in the spinal cord of rat.</p><p><b>METHODS</b>The effects of intrathecal injection of NK1 receptor agonist Sar-SP and antagonist CP-96345 and non-NMDA receptor agonist NMDA and antagonist 6, 7-dinitro-1,4-dihydro-quinoxaline-2,3-dione (DNQX) on the cardiosomatic reflex were observed in rats. The changes of the cardiosomatic reflex were monitored by observing the electromyogram (EMG) responses of the dorsal spinotrapezius muscle to intrapericardial bradykinin (BK) injection.</p><p><b>RESULTS</b>Intrathecal injection of Sar-SP significantly facilitated EMG responses to intrapericardial BK injection (P<0.05), which was completely blocked by intrathecal injection of NK1 antagonist CP-96345. Similarly, intrathecal injection of NMDA obviously facilitated the EMG responses (P<0.05), which was partially reversed by intrathecal injection of non-NMDA receptor antagonist DNQX. Intrathecal injection of Sar-SP along with NMDA significantly increased EMG as compared with single administration of Sar-SP or NMDA (P<0.05).</p><p><b>CONCLUSION</b>The spinal cord levels of NK1 receptor and non-NMDA receptor are involved in the modulation of the cardiosomatic reflex in rats.</p>

Ventrolateral periaqueductal gray metabotropic glutamate receptor subtypes 7 and 8 mediate opposite effects on cardiosomatic motor reflex in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the role of ventrolateral periaqueductal gray (VL-PAG) metabotropic glutamate receptors subtype 7 and 8 (mGluR 7/8) in descending modulation of cardiosomatic motor reflex (CMR) in rats.</p><p><b>METHODS</b>AMN082 (agonist of mGluR 7) and DCPG (agonist of mGluR 8) were injected into the VL-PAG of a rat model of CMR to observe their effects in modulating CMR. The raphe magnus nucleus (NRM) or the gigantocellular reticular nucleus (Gi) was then damaged, and the changes in VL-PAG descending modulation were observed.</p><p><b>RESULTS</b>Selective activation of mGluR 7 of the VL-PAG by AMN082 obviously facilitated capsaicin (CAP)-induced CMR (P<0.05), which was suppressed by DCPG-induced mGluR 8 activation (P<0.05). These facilitatory or inhibitory effects were completely reversed by group III mGluR antagonist MSOP. Damaging the NRM of VL-PAG main relay nucleus did not significantly affect the facilitatory effect produced by AMN082 microinjection (P>0.05), but partially attenuated the inhibitory effect of DCPG microinjection (P<0.05). Both the facilitatory effect of AMN082 and the inhibitory effect of DCPG were reduced obviously after bilateral Gi damage (P<0.05).</p><p><b>CONCLUSION</b>VL-PAG mGluR 7 and mGluR 8 mediate biphasic regulation of CMR in rats probably through activation of different sub-nuclei and different neurons in the rostroventral medulla.</p>

Role of glutamate receptor subtypes in cardiac nociception in nucleus tractus solitarius in rats / 吉林大学学报(医学版)

Objective To study the role of glutamate receptor subtypes in nucleus tractus solitarius(NTS)in cardiac-somatic motor reflex (CMR)induced by intrapericardial administration of capsaicin,and to clarify the modulation mechanism of NTS to cardiac nociceptoion.Methods 60 SD rats were randomly divided into ibotenic (IBO)group, glutamate group, MK-801 group, MCGP group, MK-801 + MCPG group and DNQX group. The NTS microinjected with 130 mmol·L-1 IBO 100 nL,100,200,500 mmol·L-1 L-glutamate 100 nL,NMDA receptor antagonist 40 and 60 mmol · L-1 MK-801 100 nL, metabotropic glutamate receptors antagonist 25 and 50 mmol·L-1 MCPG 100 nL,25 mmol· L-1 MCPG 50 nL plus 40 mmol· L-1 MK-801 50 nL,non-NMDA receptor antagonist 20 and 50 mmol·L-1 DNQX 100 nL,respectively.The changes of CMR of the rats in various groups were observed.Results Compared with control group,the CMR of the rats in IBO group was decreased (P0.05).Conclusion NTS play an facilictory role in cardiac nociception,and the NMDA receptors and mGluRs receptors mediate this facilitory modulation.

Descending inhibitory modulation of nucleus raphes magnus in cardiac nociception in rats and its pathway / 吉林大学学报(医学版)

Objective To observe the cardiosomatic motor reflex (CMR)of rats, and to clarify the descending modulation of nucleus raphes magnus (NRM)in cardiac nociception and its pathway.Methods 34 male healthy SD rats were randomly divided into NRM electrical stimulation group (n=8 ), NRM stimulation combined with dorsolateral funiculus (DLF ) transection group (n= 8 ), NRM stimulation combined with antagonist of 5-hydroxytryptamine (5-HT)methysergide intrathecal administration group (n=18).The rat model of CMR was established through inj ecting capsaicin into the pericardial sac of the rats in various groups. The electromyogram (EMG) response of dorsal spinotrapezius muscle was used as detection index, and by placing the stimulation electrode in NRM and (or)intrathecal catheterization, the descending inhibitory modulation of NRM in CMR and the influence of DLF tansection or methysergide intrathecal administration in descending inhibitory modulation of NRM were observed.Results Compared with before stimulation,the EMG response was decreased after NRM electrical stimulation (75 μA) (P 0.05 ). In addition, after intrathecal administration of methysergide,the EMG response after NRM stimulation was significantly increased compared with before intrathecal treatment of methysergide (P<0.05),but it was still significantly smaller than that of its control (P<0.05). Conclusion Cardiac nociception evoked by capsaicin stimulation is subject to descending inhibitory modulation from NRM,and the descending inhibition from NRM is conveyed via the DLF and partially mediated by endogenous 5-HT system.

Molecular mechanisms involved in curcumol induced apoptosis in human gastric carcinoma cell line BGC823 / 中华普通外科杂志

Objective To investigate the effect of curcumol on apoptosis of human gastric carcinoma cell line BGC823 and the molecular nechanisms.Methods BGC823 cells were cultured and treated with different curcumol concentration (12.5,25,50 and 100 mg/L) for 24 h and 48 h,and the growth inhibition were tested by thiazolyl blue terazolium bromide (MTF) assay.Flow cytometry (FCM) were used to measure the cell apoptosis rate and cell cycle of BGC823 cells.Caspase-3 activity was assessed by colorimetric assay.Cells treated with 100 mg/L curcunol for 48 h were collected and subjected to RTPCR and Western blot assays for the expression of Caspase-3,Bcl-2,Bax and Survivin.Results There was a time-and dose-dependent inhibition of cell proliferation of BGC823 cells by curcumol.Tbe cells in G0/G1 phase increased,and in S phase decreased on exposure to curcumol for 24 h.FCM analysis also indicated that the apoptosis rate of BGC823 cells increased in dose-dependent manner (P ＜ 0.05).Curcumol increased the activity of Caspase-3 dose-dependently (P ＜ 0.05).RT-PCR and Western blot indicated that curcumol decreased Bcl-2 and Survivin expression as well as increased Caspase-3 and Bax expression (P ＜ 0.05).Conclusions Curcumol inhibits BGC823 cell growth,arresting cells in G0/G1 phase and inducing cell apoptosis.The mechanism may be related with increasing the activity of Caspase-3,down-regulating the expression of Bcl-2 and Survivin,and up-regulating the expression of Caspase-3 and Bax.

Descending modulation of cardiac nociception by the rostral ventromedial medulla in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the descending modulation of cardiac nociception by the rostral ventromedial medulla (RVM) in rats.</p><p><b>METHODS</b>A rat model of cardiosomatic motor reflex (CMR) was established by injecting capsaicin into the pericardial sac to induce cardiac nociception, and the electromyogram (EMG) response of the dorsal spinotrapezius muscle was studied. The RVM was electrically stimulated (25, 75 and 100 µA) or destroyed to examine whether RVM exerted descending modulation on cardiac nociception.</p><p><b>RESULTS</b>Electrical stimulation of the RVM at 8 sites produced intensity-dependent inhibition of EMG responses to noxious cardiac stimulus (F[2,21]=43.188, P=0.001). Electrical stimulation at 3 sites caused facilitated EMG responses, but the increased magnitude of the EMG was not dependent on stimulation intensity (F[2,6]=0.884, P=0.461). Stimulation at 11 sites produced biphasic effects: at a low intensity (25 µA), the elicited EMG magnitude was significantly larger than baseline (P<0.05), and at greater intensities (75/100 µA), the stimulation caused suppression of the EMG magnitude to a level significantly lower than the baseline (P<0.05). Electrolytic lesion of the RVM resulted in significantly increased EMG responses compared with the baseline and sham lesion group.</p><p><b>CONCLUSION</b>Cardiac nociception evoked by capsaicin stimulation is subjected to descending biphasic modulation by the RVM, which produces predominantly descending inhibition on heart pain.</p>

The effects of soluble epoxide hydrolase inhibitors on cholesterol efflux in adipocytes / 中华内科杂志

Objective To observe the effects of soluble epoxide hydrolase inhibitors tAUCB on cholesterol efflux in adipocytes. Methods 3T3-L1 preadipocytes were induced to differentiation and maturation. Cells were stimilated with 100μg/L LPS after starved for 24 hours, then tAUCB in various concentrations(1 ,10,50,100 μmol/L)were added for 24 h, or incubated with the peroxisome proliferator activated receptor gamma (PPARy) antagonist GW9662 (5 μmol/L).0μmol/L tAUCB treated group was taken as empty control. After then, the mRNA expression of PPARγ and adenosine triphosphate binding cassette transporter Al (ABCA1) in cells were determined via realtime-PCR, the amounts of protein expression of PPARγand ABCA1 in cells were detected by Western blot, the efflux rates of 3H-cholesterol in cells were detected by means of liquid scintillation counter. Results tAUCB could dose-dependently increase the apolipoprotein A1 (apoA1)-mediated cholesterol efflux in adipocytes. After stimulated by 1, 10,50,100 μmol/L tAUCB, cholesterol efflux rates were (5.93±0.66) %, (7.40 ± 0. 43) %, (8. 30 ±0. 34)% ,(9.77±0.42)% respectively, there were significant difference after treated by 10-100 μmol/L tAUCB compared with control(5.67±0.17)%(P＜0.05). With the concentration of tAUCB increased,ABCA1, PPAR mRNA and protein expression were also dose-dependently up-regulated. GW9662 could significantly inhibit the effects of tAUCB, and then reduce the cholesterol efflux and the expression of PPARγ and ABCA1 in adipocytes. Conclusions tAUCB could up-regulate PPARγ expression in adipocytes, and promote the cholesterol efflux of adipocytes via apoA1-ABCA1 pathway, which might decrease the cellular cholesterol accumulation in adipocytes.

Effect of long-term nitrous oxide inhalation on the cardiac function in rats / 西安交通大学学报(医学版)

Objective To observe whether or not long-term inhalation of nitrous oxide can affect the cardiac function in rats. Methods Sprague-Dawley rats of either sex were randomly divided into four groups. Group A: inhaled common air for 50 days as control; Group B: inhaled 500mL/L N_2O for 15 days, two hours every day; Group C: inhaled 500mL/L N_2O for 30 days, two hours every day; Group D: inhaled 500mL/L N_2O for 50 days, two hours every day. Float glass intracellular microelectrode recording technique was used for observation of the duration (MAPD_(90), MAPD_(50) and MAPD_(20)) and amplitude of action potentials (APs) of left ventricular muscle cells in vitro. Angiotensin-2 (Ang-2) and eNOS were detected by immunohistochemical technique. Results ① Compared with that in Group A, the Aps duration of left ventricular muscle cells (MAPD) in Group B had no significant change while the MAPDs in Group C and Group D were extended significantly. There were no significant differences among the four groups in Aps amplitude. ② The expression of Ang-2 did not differ significantly between Group B and Group A. The expression level was higher in Group C and D than in Group A. ③ The expression level of eNOS was significantly lower in Group C and D than in Group A (P<0.05). Conclusion Long-term inhalation of N2O can significantly affect the cardiac function in rats, which may be related to higher expression of AngⅡin the heart induced by the long-time excitation of sympathetic nerves.

Effect of angiotensin II receptor subtype I on the firing rate in catecholaminergic tumor cells / 西安交通大学学报·英文版

Objective: To study the action of brain angiotensin II (Ang II) receptors and underlying intracellular mechanism in the catecholaminergic system (CATH) Methods: Action potentials (APs) of the primary co-cultured catecholaminergic tumor (CATH. a) cells were recorded with the whole-cell patch clamp configuration in current clamp mode. Expression of Ang II receptors subtypes (AT1 and AT2) was detected by RT-PCR technique. Results: The differentiated CATH. a cells represented a neuron-like characterization. All CATH, a cells expressed mRNA encoding both Ang II AT1 and AT 2 receptor subtypes. Ang II increased the firing rate in the CATH. a cells, which was inhibited completely by addition administration of the AT 1 but not AT2 receptor antagonist, and partially by using the inhibitors of signal molecules, U73122 (10 μmol · L-1), or KN-93 (10 μmol · L-1), or calphostin C (10 μmol · L-1). Conclusion: Ang II increases firing rate in CATH. a cells via AT1 receptor. The CATH. a cells expressing functional AT1 and AT2 receptor subtypes may be of general utility for the study of the Ang II receptor-induced modulation of brain catecholaminergic system.

FOLLICULO-STELLATE CELLS OFTHE RAT ANTERIOR PITUITARY RESPONDED TO ANGIOTENSIN Ⅱ BY INCREASING INTRACELLULAR CONCENTRATION / 药物分析学报

Objective The main purpose of this study was to investigate whether the folliculo-stellate cells (FSC) respond to angiotensin(Ang) Ⅱ by increasing intracellular free concentration ([]i) ,and where the o-rigin of mobilization is if that has occurred. Methods Pituitary cells in primary culture were prepared from male Wister rats(250g) by a conventional method and cultured in MEM supplemented with 4％ normal rat serum. Af-ter 2 days in culutre,cells were loaded with 1 μmol/L fura-PE3/AM for 1 h and subjected to a ment with Quanti Cell 700 system. Excitation wavelengths of 340 and 380 nm were selected by means of a computer-controlled filterwheel. Results The of FSC in the rat anterior pituitary was elevated by Ang Ⅱ. The eleva-tion of of FSC induced by 0. 1,1.0,10 and 100 nmol/L Ang Ⅱ was (56.33±6.18), (117.07± 36.07), (175.59 ± 40.01 ) and (216.02 ±11.52) nmol/L, respectively. The increase of of FSC induced by 100nmol/L Ang Ⅱ was not influenced by the medium without (0Ca),but significantly suppressed by thapsigargin (TG),an inhibitor of ATPase. The rate of responsive FSC to Ang Ⅱ (100 nmol/L) was 61.84％ which was obviously higher than that of pituitary endocrine cells (43.49％). Conclusion The present experiment demonstrates that the FSC in the rat anterior pituitary responds to Ang Ⅱ by increasing [which raises the possibility that Ang Ⅱ re-leased from either lactotrophs or gonadotrophs affects FSC through paracrine mechanism. The elevation of [induced by Ang Ⅱ presents a dosage-dependent relation, and is possibly because of the release of from an intra-cellular pool (s). Fashions of release are relative to the concentration of Ang Ⅱ. The results indicate that Ang Ⅱ functions as a paracrine factor among pituitary cells including FSC.

THE INHIBITORY EFFECT OF STIMULATION IN PERIAQUEDUCTAL GREY ON NEURONS IN SPINAL DORSAL HORN AND ITS RELATION TO PAG-CDP / 西安交通大学学报(医学版)

The cord dorsum potential evoked by stimulation in the ventrolateral aspect of periaqueductal grey (PAG-CDP) was recorded from the dorsal surface of the spinal lumbosacral cord in rats. PAG stimulation with the same parameters as for producing PAG-CDP inhibited the C discharges of convergent neurons in spinal dorsal horn. There was a positive correlation between the time course of the inhibitory effect of PAG on convergent neurons and the duration of the slow wave of PAG-CDP. a positive correlation also presented between the latencies of the PAG inhibition and the slow wave. Furthermore, the PAG inhibition did not appear when the intensity of PAG stimulation was below the threshold of PAG-CDP. These results indicate that the presynaptic inhibition is involved in the PAG inhibition of the C discharges of convergent neurons in spinal dorsal horn.

A PRELIMINARY REVIEW OF EMG BIOFEEDBACK FOR INSONIA PATIENTS / 西安交通大学学报(医学版)

32 cases of insomniacs were treated by using EMG biofeedback. The total efficierky was 84.4%. The result indicated that the curative effect of the therapy was satisfactory. Furthermore this paper mentioned the advantages of the therapy and points for attention. Also the principle of the treatment was discussed.