1.Cardiac responses induced by nicotinic activation of canine right atrial ganglionated plexus
Bingxiang YUAN ; Bingwen WANG ; Yongxiao CAO
Chinese Pharmacological Bulletin 1986;0(05):-
It was found that there were 31?s 13 ganglia or 1983 ?s 331 neurons ( n = 6) in canine right atrial ganglionated plexus (RAGP). Nicotine (100 ?g) was administered to the plexus in 30 anesthetized open-chest dogs. Either positive or negative inotropic and chronotropic responses were elicited. Control injections of 0. 1 m1 NS into RAGP and injections of nicotine (100 ?g and 200?g) did not elicite any cardiac responses. Following acute decentralzation of hearts, nicotine (100 ?g ) was againadministered to RAGP. Some positive and negative responses were still elicited, but frequency of the responses was reduced. It is concluded that nicotine can directly activate efferent sympathetic and parasympathetic neurons of RAGP. and indirectly activate them by stimulation of afferent neurons, these nicotine sensitive cardiac neurons can modulate cardiac function in ifferent tendencies.
2.The pharmacological mechanism of gastrodin on calcitonin gene-related peptide of cultured rat trigeminal ganglion.
Guogang LUO ; Wenjing FAN ; Xingyun YUAN ; Bobo YUAN ; Shemin Lü ; Yongxiao CAO ; Cangbao XU
Acta Pharmaceutica Sinica 2011;46(12):1451-6
The Chinese herbal medicine Tianma (Gastrodia elata) has been used for treating and preventing primary headache over thousands of years, but the exact pharmacological mechanism of the main bioactive ingredient gastrodin remains unclear. In present study, the effects of gastrodin on calcitonin gene-related peptide (CGRP) and phosphorylated extracellular signal-regulated kinase1/2 (pERK1/2) expression were observed in rat trigeminal ganglion (TG) after in vitro organ culture to explore the underlying intracellular mechanism of gastrodin on primary vascular-associated headache. CGRP-immunoreactivity (CGRP-ir) positive neurons count, positive area, mean optical density and integrated optical density by means of immunohistochemistry stain were compared at different concentrations of gastrodin, which was separately co-incubated with DMEM in SD rat TG for 24 hours. Only at 5 or 10 mmol L(-1) concentration, gastrodin demonstrated significantly concentration-dependent reduction of CGRP-ir (+) expression and its action closed to 1.2 mmol L(-1) sumatriptan succinate. While at 2.5, 20, and 40 mmol L(-1) concentration, gastrodin did not show remarkable effects on CGRP-ir (+) expression. The optimal concentration of gastrodin (5 and 10 mmol L(-1)) similarly inhibited CGRP-mRNA expression level separately compared with 1.2 mmol L(-1) sumatriptan succinate and 10 micromol L(-1) flunarizine hydrochloride, which was quantitatively analyzed by real-time PCR (RT-PCR). pERK1/2 level was examined by Western blotting after co-cultured with optimal concentration of gastrodin and effective specific ERK1/2 pathway inhibitors PD98059, U0126. The result indicated that gastrodin significantly reduced pERK1/2 protein actions similarly to ERK1/2 pathway specific blockade. It suggests ERK1/2 signaling transduction pathway may be involved in gastrodin intracellular mechanism. This study indicates gastrodin (5 and 10 mmol L(-1)) can remarkably reduce CGRP-ir (+) neuron, CGRP-mRNA and pERK1/2 expression level in cultured rat TG, with its actions similar to the effective concentration of sumatriptan succinate, flunarizine hydrochloride and specific ERK1/2 pathway blocker. The intracellular signaling transduction ERK1/2 pathway may be involved in the gastrodin reducing CGRP up-regulation in rat TG after organ culture.
3.Sumatriptan down-regulates calcitonin gene-related peptide expression via extracellular signalregulated 1/2 and c-Jun N-terminal kinase signaling transduction pathways in rat trigeminal ganglion after organ culture
Guogang LUO ; Bobo YUAN ; Wenjing FAN ; Xingyun YUAN ; Kang HUO ; Shemin LV ; Yongxiao CAO ; Cangbao XU
Chinese Journal of Neurology 2012;45(7):511-515
Objective To explore the effects of sumatriptan on the modulation of calcitonin generelated peptide(CGRP) expression and its involving intracellular signaling transduction mechanisms in rat trigeminal ganglion(TG) after organ culture.Methods Using organ culture in vitro model,54 isolated TGs of SD rats were randomly divided into fresh group ( n =6 ),control group ( n =6 ) and experimental group (n =42,6 TGs for each subgroup).Experimental group included seven subgroups,which were respectively pretreated with four different concentrations of sumatriptan,specific inhibitors of extracellular signalregulated kinases 1/2 (ERK1/2) pathway (U0126 and PD98059 ),and the inhibitor of c-Jun N-terminal kinase (JNK) (SP600125).After co-cultured with above intervention agents for 24 h,CGRP-immunoreactivity (CGRP-ir) positive neurons and CGRP-mRNA expression levels were quantified by immunohistoehemistry stain and real-time polymerase chain reaction,respectively.Phosphorylated ERK1/2 (pERK1/2) and JNK (pJNK) proteins levels were determined by Western-blotting method.Results The CGRP-ir ( + ) neurons expression levels were significantly increased after 24 h organ culture.However,0.10 and 0.50 mg/ml concentrations of sumatriptan remarkably decreased the CGRP-ir ( + ) neurons expression levels.The positive cell percentage,positive optic area,integrated optical density,mean optical density and CGRP-mRNA expression level in TG were significantly reduced than control groups (tPCP =8.652,26.382; tarea =6.220,13.917; tIA =5.606,15.904; tM14 =2.661,21.748; tmRNA =8.032,15.675.P < 0.05 ).The CGRP-mRNA expressions were significantly down-regulated after co-incubation with concentration of 0.50 mg/ml sumatriptan for 24 h in TG of SD rat ( P <0.05 ).The levels of pERK1/2 and pJNK protein kinase detected by Western-blotting were significantly reduced by 0.50 mg/ml concentration of sumatriptan,the degrees of which were closed to the ERK1/2 and JNK pathway specific blockers.Conclusion It suggests that the optimal concentration of sumatriptan significantly down-regulates CGRP over-expression via intracellular ERK1/2 and JNK signaling transduction pathways in TG after organ culture.
4.Correlation analysis between vitamin A, D and E levels with the altitude, seasonal variation and other factors in children with 0-6 years old in Tibetan Plateau of Ganzi Prefecture
Ping HUANG ; Xinmei LIN ; Quansheng WANG ; Gang KE ; Zhengrong WEI ; Duping GUO ; Xueguo BA ; Yongxiao YUAN ; Qun WANG ; Hongyan DING ; Maoyun HE ; Ligui XIAN ; Liping ZHANG ; Yufei WANG ; Lianhui YU ; Kehong KUANG ; Qingping LUO ; Zhu CHEN ; Hongmei LI ; Jing LUO ; Yilan XU
Chinese Journal of Applied Clinical Pediatrics 2021;36(22):1736-1741
Objective:To detect serum levels of vitamin A (Vit A), vitamin D(Vit D)25-hydroxy vitamin D[25-(OH)D] and vitamin E(Vit E) in children aged 0-6 years in Tibetan Plateau of Garzi Prefecture, thus providing references for physical examinations and prevention of 4 key diseases (rickets, malnutrition anemia, pneumonia and diarrhea) in children in plateau areas by relevant government departments.Methods:A total of 2 122 children who participated in physical examination in 12 townships of Xiangcheng County and 14 townships of Daocheng County, Garzi Tibetan Autonomous Prefecture, Sichuan Province from April 2017 to April 2019 with 0-6 years old were recruited for surveying physical measurements and collection of venous blood.Serum Vit A and Vit E levels were detected by high performance liquid chromatography.Serum levels of 25-(OH)D were detected by high performance liquid chromatography tandem mass spectrometry.The relationship between Vit A, Vit E and 25-(OH)D levels with the gender, age, seasonal change and altitude was analyzed.Results:The serum Vit A level, subclinical Vit A deficiency rate and marginal vitamin A deficiency rate were(1.05±0.27) μmol/L, 8.15%(173/2 122 cases) and 45.99%(976/2 122 cases), respectively in 2 122 children with 0-6 years old.There were significant differences in the serum Vit A level, the subclinical Vit A deficiency rate and the marginal vitamin A deficiency rate in children with different ages, seasons and altitudes (all P<0.05). The serum level of 25-(OH)D and 25-(OH)D deficiency rate insufficient rate were (24.65±6.45) ng/L, 6.03%(128/2 122 cases) and 16.59%(352/2 122 cases), respectively.There were significant differences in the serum level of 25-(OH)D, 25-(OH)D deficiency rate and 25-(OH)D insufficient rate in children with different ages and seasons (all P<0.05). The mean serum Vit E level, Vit E deficiency rate and Vit E insufficient rate were (7.81±1.74) mg/L, 2.78%(59/2 122 cases) and 29.59%(628/2 122 cases), respectively.There were significant differences in serum Vit E level, Vit E deficiency rate and Vit E insufficient rate in children with different ages and seasons (all P<0.05). The mean serum levels of Vit A and Vit D remained the lowest before the age of 1 year, and their deficiencies at this age were the most significant.The mean serum level of Vit E remained the lowest in >1-2 years old, and its deficiency and insufficient at this age were the most significant.Vit A, D and E levels were significantly affected by seasonal changes, which were significantly higher in the summer than in the spring, autumn and winter.In addition, Vit A and 25-(OH)D were significantly affected by the altitude, which were the lowest above 4 km altitude. Conclusions:The overall serum levels of Vit A, 25-(OH) D and E in children with 0-6 years old in Tibetan Plateau areas of Ganzi Prefecture are lower than those in plain areas.Vit A, 25-(OH) D and Vit E levels significantly differed in the age, season and altitude, which are related to the lack of local resources, insufficient maternal nutrition during pregnancy and insufficient intake after birth, as well as temperature and light caused by changes in local seasons and altitude.Therefore, it is necessary to make reasonable supplements during pregnancy to prevent vitamin deficiency.