BACKGROUND： Learning and memory processes are accompanied by complex neuropathological and biochemical changes. Free radicals play an important role in learning and memory damage. OBJECTIVE： To observe the effects o...BACKGROUND： Learning and memory processes are accompanied by complex neuropathological and biochemical changes. Free radicals play an important role in learning and memory damage. OBJECTIVE： To observe the effects of polygonatum sibiricum polysaccharide （PSP） in comparison with vitamin 12 on inhibiting free radical damage, as well as improving the degree of cerebral ischemia and learning and memory in a scopolamine-induced mouse model of dementia. DESIGN： Randomized controlled animal study. SETTINGS： Department of Pharmacology, Taishan Medical College; Shandong Jewim Pharmaceutical Co., Ltd. MATERIALS： A total of 105 healthy Kunming mice, comprising 90 males and 15 females that were clean grade, were provided by the Animal Center of Taishan Medical College. PSP （extracted and purified by Huangjing, Taishan） was provided by the Department of Traditional Chinese Medicine, Taishan Medical College （purity of 79.6% by using a phenol-concentrated sulphate acid method）, and hydrogen bromine acid scopolamine injection solution （SCO） by Shanghai Hefeng Pharmaceutical Co., Ltd. METHODS： This study was performed at the Pharmacological Laboratory of Taishan Medical College from March to June 2007. （1） A total of 75 healthy Kunming male mice of clean grade were randomly divided into a normal control group, positive control group, and low-dosage and high-dosage PSP groups, with 15 mice in each group. Mice in both the low-dosage and high-dosage PSP groups were intragastrically administered 0.5 g/kg and 2.0 g/kg PSP, respectively. Mice in the positive control group were intragastrically administered 0.5 g/kg vitamin 12. In addition, mice in both the normal control group and model group were intragastrically administered the same volume of saline, respectively, once a day for 7 consecutive days. One hour after the final administration on day 6, mice in the positive control group, model group, low-dosage and high-dosage PSP groups were subcutaneously injected with 3.0 mg/kg SCO, while mice in the normal control group were subcutaneously injected with the same volume of distilled water. Ten minutes later, the step test was employed to measure memory. The training was performed 5 times, with 30-minute intervals between 2 sets. If the mice remained on the platform （latent period） for 30 minutes, they were determined to have learned the task. An eligible percentage was then recorded. Twenty-four hours later, the number of error responses from each mouse was recorded in a 5-minute period, based on the above-mentioned parameters. Mice were sacrificed under anesthesia. The activities of glutathione hyperoxide enzyme （GSH-Px）, superoxide dismutase （SOD）, and the content of malondialdehyde （MDA） were assayed using an UV spectrophotometer. （2） The remaining 30 healthy Kunming mice of both genders were randomly divided into 3 groups, including control group, low-dosage PSP group, and high-dosage PSP group, with 10 mice in each group. Mice in both the low-dosage and high-dosage PSP groups were intragastrically administered 0.5 g/kg and 2.0 g/kg PSP, respectively, while the mice in the control group were perfused with the same volume of saline. Forty minutes later, the mice under superficial anesthesia were decapitated, and the number and duration of mouth-opening breaths of the isolated mouse head were immediately recorded. MAIN OUTCOME MEASURE： （1） Numbers of error responses within 5 minutes on the platform. （2） GSH-Px and SOD activity, as well as MDA content in mouse brain tissue. （3） Numbers and duration of mouth-opening breaths of the isolated mouse head. RESULTS： Of the 105 Kunming experimental mice, two mice died due to electric shock during the step-down test, therefore, a total of 103 mice were involved in the final analysis. （1） Effects of PSP on learning in mice： The eligible percentage in the high-dosage PSP group was higher than the control group at the 3rd and 5th training sessions （P 〈 0.05）. （2） Effects of PSP on memory in mice： The number of errors in the step-down test in the model group was higher than in the normal control group （P 〈 0.01）. Compared to the model group, the number of errors in the step-down test was lower in both the low-dosage and high-dosage PSP groups （P 〈 0.01）. （3） Effects of PSP on amount of GSH-Px, SOD, and MDA in mouse brain tissue： SOD and GSH-Px activity was higher in both the low-dosage and high-dosage PSP groups than in the model group. MDA content was lower in the high-dosage PSP group, compared to the model group. GSH-Px activity in the brain tissue of the high-dosage PSP group was similar to the positive control group （P 〉 0.05）. （4） Effects of PSP on acute cerebral ischemia in mice： The low-dosage PSP, and in particular the high-dosage PSP, prolonged the number and duration of mouth-opening breaths of the isolated mouse head （P 〈 0.05, 0.01）. CONCLUSION： PSP can improve learning and memory in a scopolamine-induced mouse model of dementia by reducing the damaging effects of cerebral ischemia and anti-oxidation. In addition, the effects are dose-dependent and are similar to those provided by vitamin E.展开更多
The present study observed the action of 1H-indole-2, 3-dione （isatin） on Bax protein expression in the substantia nigra of a Parkinson＇s disease animal model. Parkinson＇s disease-like behaviors were induced in C5...The present study observed the action of 1H-indole-2, 3-dione （isatin） on Bax protein expression in the substantia nigra of a Parkinson＇s disease animal model. Parkinson＇s disease-like behaviors were induced in C57BL/6J mice treated with 1-methyl-4-phenyl-1,2, 3, 6-tetrahydropyridine （MPTP） Bax protein expression was significantly reduced in isatin （100, 200 mg/kg）-pretreated mice. Results demonstrate that isatin plays a neuroprotective role in mice treated with MPTP by down-regulating Bax protein expression.展开更多
BACKGROUND： It is proved that the onset of Parkinson disease companies with neuronal apoptosis of dopamine in substantia nigra of midbrain. Previous researches on neuronal apoptosis of dopamine were analyzed on their...BACKGROUND： It is proved that the onset of Parkinson disease companies with neuronal apoptosis of dopamine in substantia nigra of midbrain. Previous researches on neuronal apoptosis of dopamine were analyzed on their consecutive tissue sections with immunohistochemical single-labeling method, immunofluorescence and electron microscope, and there are significant differences.OBJECTIVE ： To observe the feasibility of neuronal apoptosis of dopamine with in situ end labeling and tyrosine-hydroxylase antibody immunohistochemical double-labeling staining technique.DESIGN ： Controlled study.SETTING： College of Pharmacology of Taishan Medical College; College of Management of Taishan Medical College. MATERIALS ： Wistar rats with 2 weeks old and of clean grade were provided by the Animal Center of Taishan Medical College. In situ end labeling kit （terminal deoxynucleotidyl transferase, mixed reactive solution of nucleotide, transfusion-POD）, monoclonal antibody of rat antibody against tyrosine hydroxylase （Boehriuser）. METHODS： The experiment was completed at the Pharmacological Laboratory of Taishan Medical College from February to December 2005. Tissue from midbrain of rats was taken out to make paraffin sections to observe the neuronal apoptosis of dopamine under microscope with in situ end labeling and tyrosine-hydroxylase antibody immunohistochemical double-labeling staining technique.MAIN OUTCOME MEASURES ： Neuronal apoptosis of dopamine with in situ end labeling and tyrosine-hydroxylase antibody immunohistochemical double-labeling staining technique. RESULTS： ① After double-labeling staining, two kinks of positive products were observed in neurons of dopamine which were suffered from apoptosis. One stained with tyrosine hydroxylase was hyacinthine, and the other stained with in situ end labeling was buffy. Cells of positive products stained with in situ end labeling shaped as strap and bend and was distributed in clustering. Cytoplasm was hyacinthine, staining was symmetrical, and cellular ecphyma was observed. Nucleus was stained vacantly which was coincidence with form of neurons of dopamine. ②Apoptosis showed strictly in cytoplasm and nucleus at the aspect of morphology. Cytoplasm stained with in situ end labeling was hardly to recognize because of the usage of double-labeling staining technique, but nucleus was still characterized by apoptosis. The behavior of positive products stained with in situ end labeling was described as following： nucleus was buffy; karyopycnosis was round and irregular; caryotin was integrated into clump which was distributed at the border of nucleus and shaped as demilune and anular; positive signals were limited in nucleus and coincidence with morphological changes of apoptosis. However, blue and positive products were observed in cytoplasm of neurons of dopamine which did not occur apoptosis, and the nucleus was not labeled. Therefore, processing apoptosis of neurons of dopamine could be recognized. CONCULSION： Double-labeling staining technique can be used to correctly reveal histological and morphological changes of neuronal apoptosis of dopamine during its onset and development.展开更多
BACKGROUND： Ketamine is a noncompetitive antagonist of N-methyI-D-aspartic acid receptor. Some researchers suggest that N-methyI-D-aspartic acid （NMDA） receptor is closely related to epileptic attack. OBJECTIVE： T...BACKGROUND： Ketamine is a noncompetitive antagonist of N-methyI-D-aspartic acid receptor. Some researchers suggest that N-methyI-D-aspartic acid （NMDA） receptor is closely related to epileptic attack. OBJECTIVE： To observe inhibitory effect of ketamine on lighting amygdala of rats and analyze pathway of anti-lighting. DESIGN： Randomized controlled animal study SETTING： Department of Pharmacology and Department of Management, Pharmacological College of Taishan Medical College; Department of Pharmacology, Medical College of Qingdao University. MATERIALS： Sixty adult female Wistar rats, of clean grade, weighing 180-200 g, were provided by Animal Center of Qingdao Institute of Drug Control. Ketamine hydrochloride was provided by the First Pharmacological Factory of the First Biochemical Pharmacology Company of Shanghai, and nicardipine, an antagonist of calcium ions, was provided by Sigma Company. METHODS： The experiment was completed in the Department of Pharmacology, Medical College of Qingdao University from March to November 2004. ① Model establishing： After anesthesia, left and right amygdalas were inserted with double electrodes. The top was separated about 0.25 mm, and the other end was welded with a micro-plug, respectively. Electrode and micro-plug were fixed with dental base acrylic resin powder at the surface of cranium. Two weeks after recovery, right amygdala was stimulated with constant current once a day. According to Racine technique, attacking intensity was divided into 5 grades： grade I： closing eyes, a little tingling of beards and twitching face; grade Ⅱ ： nodding, chewing accompanying with twitching face; grade Ⅲ ： raising one of a forelimb and clonus; grade Ⅳ： standing accompanying with bilateral forelimbs; grade Ⅴ： standing accompanying with falling down. Rats with grades Ⅳ and Ⅴ were used to establish secondarily generalized epilepsy. If 3 successive attacks of grade V were observed, the lighting was to be successful. ② Effect of ketamine on lighting amygdala of rats： A total of 24 rats were divided into 3 groups with 8 in each group according to lot technique. Rats in the 3 groups were intraperitoneally injected with 30.0, 10.0 and 5.0 mg/kg ketamine, respectively; 30 minutes later, after-discharging value was measured and rats were stimulated with constant current; otherwise, other parameters were not changed. In addition, after-discharging duration and Racine grade were recorded. ③ Effect of ketamine and amygdala on lighting attack of rats： Another 24 rats were divided into 3 groups according to lot technique and intraperitoneally injected with 5.0 mg/kg ketamine, 2 mg/kg nicardipin and 5.0 mg/kg ketamine ＋ 2 mg/kg nicardipin, respectively. The injected volume was 2 mL/kg and after-discharging duration and Racine grade were recorded before and after administration. MAIN OUTCOME MEASURES： Effect of ketamine with various dosages and ketamine ＋ nicardipine with ineffective dosages on after-discharging duration and Racine grade after lighting amygdala. RESULTS; Among 50 rats, 48 with successful lighting amygdale of dpileptic model were involved in the final analysis. ① Effect of ketamine on lighting amygdala of rats： The after-discharging duration was （52.4±16.5） and （28.4±21.4） s after administration and （65.6±10.3）, （65.5±13.2） s before administration, and there was significant difference （P〈 0.05-0.01）; Racine grade was 3.6±1.19 and 2.0±0.99 after administration and 5.0±0 and 5.0±0 before administration, and there was significant difference （P 〈 0.05-0.01）. However, if the injected dosage was 5.0 mg/kg, after-discharging duration and Racine grade were similar before and after administration （P 〉 0.05）. ② Effect of ketamine ＋ nicardipine on lighting attack： When rats were injected with 5 mg/kg ketamine or 2 mg/kg nicardipine, respectively, after-discharging duration was （63.8±11.7）, （63.0±35.3） s before administration and （63.6±12.5）, （59.8±38.8） s after administration, and there was no significant difference （P 〉 0.05）. Meanwhile, Racine grade was 4.6±0.5 and 5.0±0 before administration and 5.0±0 and 5.0±0 after administration, and there was no significant difference （P 〉 0.05）. When rats were injected with 5.0 mg/kg ketamine ＋ 2.0 mg/kg nicardipine, after-discharging duration and Racine grade were （42.3±9.7） s and 3.1±0.7, respectively, and these were obviously shorter/lower than those before administration [（60.6±10.3） s, 5.0±0, P 〈 0.05]. CONCLUSION： Ketamine （10 and 30 mg/kg） can inhibit lighting attack of amygdale in epilepsy, but low dosage （5 mg/kg） was ineffective; however, the combination of 5.0 mg/kg ketamine and 2 mg/kg nicardipin can also inhibit lighting. Therefore, it is suspected that effect of ketamine on anti-lighting is reacted on inhibiting Ca^2＋ internal flow mediated by NMDA receptor.展开更多
The clinical utilization of doxorubicin(Dox)in various malignancies is restrained by its major adverse effect:irreversible cardiomyopathy.Extensive studies have been done to explore the prevention of Dox cardiomyopath...The clinical utilization of doxorubicin(Dox)in various malignancies is restrained by its major adverse effect:irreversible cardiomyopathy.Extensive studies have been done to explore the prevention of Dox cardiomyopathy.Currently,ferroptosis has been shown to participate in the incidence and development of Dox cardiomyopathy.Sorting Nexin 3(SNX3),the retromer-associated cargo binding protein with important physiological functions,was identified as a potent therapeutic target for cardiac hypertrophy in our previous study.However,few study has shown whether SNX3 plays a critical role in Dox-induced cardiomyopathy.In this study,a decreased level of SNX3 in Dox-induced cardiomyopathy was observed.Cardiac-specific Snx3 knockout(Snx3-cKO)significantly alleviated cardiomyopathy by downregulating Dox-induced ferroptosis significantly.SNX3 was further demonstrated to exacerbate Dox-induced cardiomyopathy via induction of ferroptosis in vivo and in vitro,and cardiac-specific Snx3 transgenic(Snx3-cTg)mice were more susceptible to Dox-induced feroptosis and cardiomyopathy.Mechanistically,SNX3 facilitated the recycling of transferrin 1 receptor(TFRC)via direct interaction,disrupting iron homeostasis,increasing the accumulation of iron,triggering ferroptosis,and eventually exacerbating Dox-induced cardiomyopathy.Overall,these findings established a direct SNX3-TFRC-ferroptosis positive regulatory axis in Dox-induced cardiomyopathy and suggested that targeting SNX3 provided a new effective therapeutic strategy for Dox-induced cardiomyopathy through TFRCdependentferroptosis.展开更多
What is already known about this topic?Sodium intake in China is among the highest in the world,the main source of which in adults is salt added during cooking.In 2012,the national average cooking salt intake was 10.5...What is already known about this topic?Sodium intake in China is among the highest in the world,the main source of which in adults is salt added during cooking.In 2012,the national average cooking salt intake was 10.5 g/d.What is added by this report?In 2018,median cooking salt intake was 6.3 g/d,which has decreased compared to that in 1991.The northsouth gap in cooking salt intake was closing over time.What are the implications for public health practice?Effective policies and interventions need to be sustained and intensified to lower cooking salt intake,thus achieving the recommended level of sodium and total salt intake.展开更多
The shape and the size of inclusions in DKDP crystal have been observed and measured microscopically. Three kinds of inclusions were found and the components of the inclusions were measured. The formation mechanisms w...The shape and the size of inclusions in DKDP crystal have been observed and measured microscopically. Three kinds of inclusions were found and the components of the inclusions were measured. The formation mechanisms were proposed and discussed.展开更多
文摘BACKGROUND： Learning and memory processes are accompanied by complex neuropathological and biochemical changes. Free radicals play an important role in learning and memory damage. OBJECTIVE： To observe the effects of polygonatum sibiricum polysaccharide （PSP） in comparison with vitamin 12 on inhibiting free radical damage, as well as improving the degree of cerebral ischemia and learning and memory in a scopolamine-induced mouse model of dementia. DESIGN： Randomized controlled animal study. SETTINGS： Department of Pharmacology, Taishan Medical College; Shandong Jewim Pharmaceutical Co., Ltd. MATERIALS： A total of 105 healthy Kunming mice, comprising 90 males and 15 females that were clean grade, were provided by the Animal Center of Taishan Medical College. PSP （extracted and purified by Huangjing, Taishan） was provided by the Department of Traditional Chinese Medicine, Taishan Medical College （purity of 79.6% by using a phenol-concentrated sulphate acid method）, and hydrogen bromine acid scopolamine injection solution （SCO） by Shanghai Hefeng Pharmaceutical Co., Ltd. METHODS： This study was performed at the Pharmacological Laboratory of Taishan Medical College from March to June 2007. （1） A total of 75 healthy Kunming male mice of clean grade were randomly divided into a normal control group, positive control group, and low-dosage and high-dosage PSP groups, with 15 mice in each group. Mice in both the low-dosage and high-dosage PSP groups were intragastrically administered 0.5 g/kg and 2.0 g/kg PSP, respectively. Mice in the positive control group were intragastrically administered 0.5 g/kg vitamin 12. In addition, mice in both the normal control group and model group were intragastrically administered the same volume of saline, respectively, once a day for 7 consecutive days. One hour after the final administration on day 6, mice in the positive control group, model group, low-dosage and high-dosage PSP groups were subcutaneously injected with 3.0 mg/kg SCO, while mice in the normal control group were subcutaneously injected with the same volume of distilled water. Ten minutes later, the step test was employed to measure memory. The training was performed 5 times, with 30-minute intervals between 2 sets. If the mice remained on the platform （latent period） for 30 minutes, they were determined to have learned the task. An eligible percentage was then recorded. Twenty-four hours later, the number of error responses from each mouse was recorded in a 5-minute period, based on the above-mentioned parameters. Mice were sacrificed under anesthesia. The activities of glutathione hyperoxide enzyme （GSH-Px）, superoxide dismutase （SOD）, and the content of malondialdehyde （MDA） were assayed using an UV spectrophotometer. （2） The remaining 30 healthy Kunming mice of both genders were randomly divided into 3 groups, including control group, low-dosage PSP group, and high-dosage PSP group, with 10 mice in each group. Mice in both the low-dosage and high-dosage PSP groups were intragastrically administered 0.5 g/kg and 2.0 g/kg PSP, respectively, while the mice in the control group were perfused with the same volume of saline. Forty minutes later, the mice under superficial anesthesia were decapitated, and the number and duration of mouth-opening breaths of the isolated mouse head were immediately recorded. MAIN OUTCOME MEASURE： （1） Numbers of error responses within 5 minutes on the platform. （2） GSH-Px and SOD activity, as well as MDA content in mouse brain tissue. （3） Numbers and duration of mouth-opening breaths of the isolated mouse head. RESULTS： Of the 105 Kunming experimental mice, two mice died due to electric shock during the step-down test, therefore, a total of 103 mice were involved in the final analysis. （1） Effects of PSP on learning in mice： The eligible percentage in the high-dosage PSP group was higher than the control group at the 3rd and 5th training sessions （P 〈 0.05）. （2） Effects of PSP on memory in mice： The number of errors in the step-down test in the model group was higher than in the normal control group （P 〈 0.01）. Compared to the model group, the number of errors in the step-down test was lower in both the low-dosage and high-dosage PSP groups （P 〈 0.01）. （3） Effects of PSP on amount of GSH-Px, SOD, and MDA in mouse brain tissue： SOD and GSH-Px activity was higher in both the low-dosage and high-dosage PSP groups than in the model group. MDA content was lower in the high-dosage PSP group, compared to the model group. GSH-Px activity in the brain tissue of the high-dosage PSP group was similar to the positive control group （P 〉 0.05）. （4） Effects of PSP on acute cerebral ischemia in mice： The low-dosage PSP, and in particular the high-dosage PSP, prolonged the number and duration of mouth-opening breaths of the isolated mouse head （P 〈 0.05, 0.01）. CONCLUSION： PSP can improve learning and memory in a scopolamine-induced mouse model of dementia by reducing the damaging effects of cerebral ischemia and anti-oxidation. In addition, the effects are dose-dependent and are similar to those provided by vitamin E.
基金a grant from Shandong Provincial Education Department, No. J08LH54
文摘The present study observed the action of 1H-indole-2, 3-dione （isatin） on Bax protein expression in the substantia nigra of a Parkinson＇s disease animal model. Parkinson＇s disease-like behaviors were induced in C57BL/6J mice treated with 1-methyl-4-phenyl-1,2, 3, 6-tetrahydropyridine （MPTP） Bax protein expression was significantly reduced in isatin （100, 200 mg/kg）-pretreated mice. Results demonstrate that isatin plays a neuroprotective role in mice treated with MPTP by down-regulating Bax protein expression.
文摘BACKGROUND： It is proved that the onset of Parkinson disease companies with neuronal apoptosis of dopamine in substantia nigra of midbrain. Previous researches on neuronal apoptosis of dopamine were analyzed on their consecutive tissue sections with immunohistochemical single-labeling method, immunofluorescence and electron microscope, and there are significant differences.OBJECTIVE ： To observe the feasibility of neuronal apoptosis of dopamine with in situ end labeling and tyrosine-hydroxylase antibody immunohistochemical double-labeling staining technique.DESIGN ： Controlled study.SETTING： College of Pharmacology of Taishan Medical College; College of Management of Taishan Medical College. MATERIALS ： Wistar rats with 2 weeks old and of clean grade were provided by the Animal Center of Taishan Medical College. In situ end labeling kit （terminal deoxynucleotidyl transferase, mixed reactive solution of nucleotide, transfusion-POD）, monoclonal antibody of rat antibody against tyrosine hydroxylase （Boehriuser）. METHODS： The experiment was completed at the Pharmacological Laboratory of Taishan Medical College from February to December 2005. Tissue from midbrain of rats was taken out to make paraffin sections to observe the neuronal apoptosis of dopamine under microscope with in situ end labeling and tyrosine-hydroxylase antibody immunohistochemical double-labeling staining technique.MAIN OUTCOME MEASURES ： Neuronal apoptosis of dopamine with in situ end labeling and tyrosine-hydroxylase antibody immunohistochemical double-labeling staining technique. RESULTS： ① After double-labeling staining, two kinks of positive products were observed in neurons of dopamine which were suffered from apoptosis. One stained with tyrosine hydroxylase was hyacinthine, and the other stained with in situ end labeling was buffy. Cells of positive products stained with in situ end labeling shaped as strap and bend and was distributed in clustering. Cytoplasm was hyacinthine, staining was symmetrical, and cellular ecphyma was observed. Nucleus was stained vacantly which was coincidence with form of neurons of dopamine. ②Apoptosis showed strictly in cytoplasm and nucleus at the aspect of morphology. Cytoplasm stained with in situ end labeling was hardly to recognize because of the usage of double-labeling staining technique, but nucleus was still characterized by apoptosis. The behavior of positive products stained with in situ end labeling was described as following： nucleus was buffy; karyopycnosis was round and irregular; caryotin was integrated into clump which was distributed at the border of nucleus and shaped as demilune and anular; positive signals were limited in nucleus and coincidence with morphological changes of apoptosis. However, blue and positive products were observed in cytoplasm of neurons of dopamine which did not occur apoptosis, and the nucleus was not labeled. Therefore, processing apoptosis of neurons of dopamine could be recognized. CONCULSION： Double-labeling staining technique can be used to correctly reveal histological and morphological changes of neuronal apoptosis of dopamine during its onset and development.
文摘BACKGROUND： Ketamine is a noncompetitive antagonist of N-methyI-D-aspartic acid receptor. Some researchers suggest that N-methyI-D-aspartic acid （NMDA） receptor is closely related to epileptic attack. OBJECTIVE： To observe inhibitory effect of ketamine on lighting amygdala of rats and analyze pathway of anti-lighting. DESIGN： Randomized controlled animal study SETTING： Department of Pharmacology and Department of Management, Pharmacological College of Taishan Medical College; Department of Pharmacology, Medical College of Qingdao University. MATERIALS： Sixty adult female Wistar rats, of clean grade, weighing 180-200 g, were provided by Animal Center of Qingdao Institute of Drug Control. Ketamine hydrochloride was provided by the First Pharmacological Factory of the First Biochemical Pharmacology Company of Shanghai, and nicardipine, an antagonist of calcium ions, was provided by Sigma Company. METHODS： The experiment was completed in the Department of Pharmacology, Medical College of Qingdao University from March to November 2004. ① Model establishing： After anesthesia, left and right amygdalas were inserted with double electrodes. The top was separated about 0.25 mm, and the other end was welded with a micro-plug, respectively. Electrode and micro-plug were fixed with dental base acrylic resin powder at the surface of cranium. Two weeks after recovery, right amygdala was stimulated with constant current once a day. According to Racine technique, attacking intensity was divided into 5 grades： grade I： closing eyes, a little tingling of beards and twitching face; grade Ⅱ ： nodding, chewing accompanying with twitching face; grade Ⅲ ： raising one of a forelimb and clonus; grade Ⅳ： standing accompanying with bilateral forelimbs; grade Ⅴ： standing accompanying with falling down. Rats with grades Ⅳ and Ⅴ were used to establish secondarily generalized epilepsy. If 3 successive attacks of grade V were observed, the lighting was to be successful. ② Effect of ketamine on lighting amygdala of rats： A total of 24 rats were divided into 3 groups with 8 in each group according to lot technique. Rats in the 3 groups were intraperitoneally injected with 30.0, 10.0 and 5.0 mg/kg ketamine, respectively; 30 minutes later, after-discharging value was measured and rats were stimulated with constant current; otherwise, other parameters were not changed. In addition, after-discharging duration and Racine grade were recorded. ③ Effect of ketamine and amygdala on lighting attack of rats： Another 24 rats were divided into 3 groups according to lot technique and intraperitoneally injected with 5.0 mg/kg ketamine, 2 mg/kg nicardipin and 5.0 mg/kg ketamine ＋ 2 mg/kg nicardipin, respectively. The injected volume was 2 mL/kg and after-discharging duration and Racine grade were recorded before and after administration. MAIN OUTCOME MEASURES： Effect of ketamine with various dosages and ketamine ＋ nicardipine with ineffective dosages on after-discharging duration and Racine grade after lighting amygdala. RESULTS; Among 50 rats, 48 with successful lighting amygdale of dpileptic model were involved in the final analysis. ① Effect of ketamine on lighting amygdala of rats： The after-discharging duration was （52.4±16.5） and （28.4±21.4） s after administration and （65.6±10.3）, （65.5±13.2） s before administration, and there was significant difference （P〈 0.05-0.01）; Racine grade was 3.6±1.19 and 2.0±0.99 after administration and 5.0±0 and 5.0±0 before administration, and there was significant difference （P 〈 0.05-0.01）. However, if the injected dosage was 5.0 mg/kg, after-discharging duration and Racine grade were similar before and after administration （P 〉 0.05）. ② Effect of ketamine ＋ nicardipine on lighting attack： When rats were injected with 5 mg/kg ketamine or 2 mg/kg nicardipine, respectively, after-discharging duration was （63.8±11.7）, （63.0±35.3） s before administration and （63.6±12.5）, （59.8±38.8） s after administration, and there was no significant difference （P 〉 0.05）. Meanwhile, Racine grade was 4.6±0.5 and 5.0±0 before administration and 5.0±0 and 5.0±0 after administration, and there was no significant difference （P 〉 0.05）. When rats were injected with 5.0 mg/kg ketamine ＋ 2.0 mg/kg nicardipine, after-discharging duration and Racine grade were （42.3±9.7） s and 3.1±0.7, respectively, and these were obviously shorter/lower than those before administration [（60.6±10.3） s, 5.0±0, P 〈 0.05]. CONCLUSION： Ketamine （10 and 30 mg/kg） can inhibit lighting attack of amygdale in epilepsy, but low dosage （5 mg/kg） was ineffective; however, the combination of 5.0 mg/kg ketamine and 2 mg/kg nicardipin can also inhibit lighting. Therefore, it is suspected that effect of ketamine on anti-lighting is reacted on inhibiting Ca^2＋ internal flow mediated by NMDA receptor.
基金supported by the National Natural Science Foundation of China(82173808,U21A20419,82270500)Natural Science Foundation of Guangdong Province(2021B1515020100,China)+3 种基金Guangzhou Basic and Applied Basic Research Project(202206080007,China)Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(2017BT01Y093,China)Guangdong Provincial Key Laboratory of Construction Foundation(2017B030314030,China)Academic promotion program of Shandong First Medical University(2019LJ003,China).
文摘The clinical utilization of doxorubicin(Dox)in various malignancies is restrained by its major adverse effect:irreversible cardiomyopathy.Extensive studies have been done to explore the prevention of Dox cardiomyopathy.Currently,ferroptosis has been shown to participate in the incidence and development of Dox cardiomyopathy.Sorting Nexin 3(SNX3),the retromer-associated cargo binding protein with important physiological functions,was identified as a potent therapeutic target for cardiac hypertrophy in our previous study.However,few study has shown whether SNX3 plays a critical role in Dox-induced cardiomyopathy.In this study,a decreased level of SNX3 in Dox-induced cardiomyopathy was observed.Cardiac-specific Snx3 knockout(Snx3-cKO)significantly alleviated cardiomyopathy by downregulating Dox-induced ferroptosis significantly.SNX3 was further demonstrated to exacerbate Dox-induced cardiomyopathy via induction of ferroptosis in vivo and in vitro,and cardiac-specific Snx3 transgenic(Snx3-cTg)mice were more susceptible to Dox-induced feroptosis and cardiomyopathy.Mechanistically,SNX3 facilitated the recycling of transferrin 1 receptor(TFRC)via direct interaction,disrupting iron homeostasis,increasing the accumulation of iron,triggering ferroptosis,and eventually exacerbating Dox-induced cardiomyopathy.Overall,these findings established a direct SNX3-TFRC-ferroptosis positive regulatory axis in Dox-induced cardiomyopathy and suggested that targeting SNX3 provided a new effective therapeutic strategy for Dox-induced cardiomyopathy through TFRCdependentferroptosis.
文摘What is already known about this topic?Sodium intake in China is among the highest in the world,the main source of which in adults is salt added during cooking.In 2012,the national average cooking salt intake was 10.5 g/d.What is added by this report?In 2018,median cooking salt intake was 6.3 g/d,which has decreased compared to that in 1991.The northsouth gap in cooking salt intake was closing over time.What are the implications for public health practice?Effective policies and interventions need to be sustained and intensified to lower cooking salt intake,thus achieving the recommended level of sodium and total salt intake.
基金This work was supported by the National Natural Science Foundation of China (Grant No. 59823003) the Natural Science Fund of Shandong Province (Grant No. Y2000F09) the Youth Foundation of State High Technology Project for ICF.
文摘The shape and the size of inclusions in DKDP crystal have been observed and measured microscopically. Three kinds of inclusions were found and the components of the inclusions were measured. The formation mechanisms were proposed and discussed.
