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J Ethnopharmacol ; 249: 112437, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31794788


ETHNOPHARMACOLOGICAL RELEVANCE: Migraine is a disabling neurovascular disorder, which increases risk of cardiovascular events and is a social burden worldwide. The present first-line anti-migraine medications can cause overwhelming side-effects, of which one includes the onset of cardiovascular disease. As one of the marketed Tibetan drugs, Ru-yi-Zhen-bao Pills (RYZBP) have been clinically used to treat cardiovascular disorders and as anti-migraine medication. However, there is currently no research exploring the anti-migraine actions of RYZBP. AIM OF THE STUDY: The current research was designed to assess the anti-migraine roles of RYZBP and explore the underlying mechanisms in a nitroglycerin (NTG)-induced migraine rat model trial. MATERIALS AND METHODS: 120 rats were randomly divided into the following six groups of 20 rats each: normal control group, model control group, positive control group, and RYZBP high/medium/low-dose groups (Ru-yi-Zhen-bao Pills; TH 1.00 g/kg, TM 0.50 g/kg and TL 0.25 g/kg). All rats were administered intragastrically for 7 consecutive days, which were subcutaneously injected with the NTG (10 mg/kg) after the last gavage (except in the normal control group). 3min after NTG treatment, 30 rats (5 rats from each group) were anesthetized and devoted to electroencephalogram(EEG) testing, which was used to evaluate the analgesic effect of RYZBP. One hour after NTG treatment, the rest of the 90 rats (15 rats from each group) were anesthetized and midbrain tissue sample was dissected. The dissection was then washed with physiological saline and collected. The histopathological changes in the periaqueductal gray(PAG) of 5 tissue samples were determined by aematoxylin-eosin (H&E) staining, as well as an estimation of substance P (SP) and neurokinin 1 receptor (NK1R) expression through immunohistochemically staining(IHC). Another 5 midbrain preparations were carried out to evaluate calcitonin gene-related peptide (CGRP), proenkephalin (PENK), SP, and cholecystokinin (CCK) expressions by real-time quantitative polymerase chain reaction (RT-qPCR). The rest of the 5 brainstem tissues were then used to measure CCK, CGRP, and opioid peptide receptor (DORR) levels by western blotting(WB). RESULTS: In the EEG test, RYZBP (TM 0.50 g / kg) treatment transformed the EEG pain-wave of the NTG-induced migraine model rats in different time period. In the mechanism assay, compared with the model control group, RYZBP pretreatment reduced inflammatory cell infiltration, fibrosis and vacuolation of neuronal cells of PAG tissue seen by HE staining. IHC experiments further showed that RYZBPTM up-regulated SP expression levels and enhanced NK1R levels in the NTG-induced migraine rats (P < 0.05). Therapeutic administration of RYZBP also increased PENK mRNA expression and DORR protein level. Both RT-qPCR and western blotting trials indicated that RYZBP treatment significantly decreased CCK and CGRP expression levels (P < 0.01 or P < 0.05) in the NTG-induced migraine rats. CONCLUSIONS: RYZBP has the potential to be an effective anti-migraine treatment through suppressing the EEG pain-wave, increasing the levels of SP, PENK, DORR and reducing expression of CCK and CGRP. Mediating the PAG anti-nociceptive channel and inhibiting central sensitization were the two potential mechanisms, which offers further evidence for clinical therapy.

Neuropsychopharmacology ; 43(11): 2320-2330, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29993042


Patients with neuropathic pain are usually accompanied by depression. Chemokine-mediated neuroinflammation is involved in a variety of diseases, including neurodegenerative diseases, depression, and chronic pain. The nucleus accumbens (NAc) is an important area in mediating pain sensation and depression. Here we report that spinal nerve ligation (SNL) induced upregulation of chemokine CCL2 and its major receptor CCR2 in both dopamine D1 and D2 receptor (D1R and D2R)-containing neurons in the NAc. Inhibition of CCR2 by shRNA lentivirus in the NAc shell attenuated SNL-induced pain hypersensitivity and depressive behaviors. Conversely, intra-NAc injection of CCL2-expressing lentivirus-induced nociceptive and depressive behaviors in naïve mice. Whole-cell patch clamp recording of D1R-positive or D2R-positive medium spiny neurons (MSNs) showed that SNL increased NMDA receptor (NMDAR)-mediated currents that are induced by stimulation of prefrontal cortical afferents to MSNs, which was inhibited by a CCR2 antagonist. Furthermore, Ccr2 shRNA also reduced NMDAR-mediated currents, and this reduction was mainly mediated via NR2B subunit. Consistently, NR2B, colocalized with CCR2 in the NAc, was phosphorylated after SNL and was inhibited by intra-NAc injection of Ccr2 shRNA. Furthermore, SNL or CCL2 induced ERK activation in the NAc. Inhibition of ERK by a MEK inhibitor reduced NR2B phosphorylation induced by SNL or CCL2. Finally, intra-NAc injection of NR2B antagonist or MEK inhibitor attenuated SNL-induced pain hypersensitivity and depressive behaviors. Collectively, these results suggest that CCL2/CCR2 signaling in the NAc shell is important in mediating neuropathic pain and depression via regulating NR2B-mediated NMDAR function in D1R- and D2R-containing neurons following peripheral nerve injury.

Depressão/metabolismo , Neuralgia/metabolismo , Núcleo Accumbens/metabolismo , Receptores CCR2/metabolismo , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Depressão/fisiopatologia , Depressão/psicologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Neuralgia/fisiopatologia , Neuralgia/psicologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Núcleo Accumbens/efeitos dos fármacos , Técnicas de Cultura de Órgãos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores
Zhonghua Yi Shi Za Zhi ; 41(2): 126-7, 2011 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-21624278


ZHENG Guanying (1842 - 1922) was a famous industrialist and educator of modern times. He is interested in medicine and dabbled in health preserving of traditional Chinese medicine and health care of western medicine which could be reflected in his books Zhongwai Weisheng Yaozhi. His opinions on mental regulation, healthy diet and daily life could be seen from this book.