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Objective:To study the protective effects of various doses of Glycyrrhizin on hippocampus of young rats with status epilepticus (SE).Methods:Lithium chloride and pilocarpine were injected intraperitoneally into male Sprague-Dawley (SD) rats (with a postnatal age of 18-21 days), so as to induce SE in rats.The rats were divided into 5 groups according to the random number table method: control group, SE group, SE+ low dose Glycyrrhizin group, SE+ medium dose Glycyrrhizin group and SE+ high dose Glycyrrhizin group.Three different doses of Glycyrrhizin (20 mg/kg, 40 mg/kg and 60 mg/kg) were injected intraperitoneally into the rats.The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in serum of SE rats were determined by enzyme linked immunosorbent assay.Quantitative real-time PCR (qRT-PCR) was used to detect the mRNA expression levels of TNF- α, IL-1β and IL-6 in hippocampus of SE rats.The expression levels of Bax, Bcl-2 and Caspase-3 in hippocampus were detected by Western blot.The damage of neurons was measured by hematoxylin and eosin (HE) staining and Nissl staining.Neurons apoptosis was examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The mitochondrial changes were observed under transmission electron microscopy.One-way ANOVA followed by Tukey post-hoc test was used for statistical analysis. Results:Compared to the control group, TNF-α[(369.69±58.07) ng/L vs. (75.46±14.64) ng/L], IL-1β[(242.27±25.23) ng/L vs. (45.29±5.90) ng/L] and IL-6[(288.15±24.60) ng/L vs. (46.59±8.80) ng/L] in the serum of SE rats were significantly up-regulated(all P<0.05). Compared to SE group, low, medium and high doses Glycyrrhizin could effectively reduce the levels of TNF-α[(216.67±8.31) ng/L, (158.81±5.03) ng/L and (113.69±12.54) ng/L vs. (369.69±58.07) ng/L], IL-1β[(131.21±5.50) ng/L, (86.60±7.79) ng/L and (65.06±4.39) ng/L vs. (242.27±25.23) ng/L] and IL-6[(150.24±9.48) ng/L, (101.70±5.85) ng/L and (91.60±2.81) ng/L vs. (288.15±24.60) ng/L] released in serum after SE occurred (all P<0.05). The neuronal damage, loss, apoptosis and mitochondrial damage were found in the hippocampus of SE rats.Glycyrrhizin could ameliorate these symptoms.Compared to the control group, Bax levels(0.57±0.01 vs. 0.14±0.01)and Caspase-3 levels(0.54±0.00 vs. 0.11±0.01)in the hippocampus of SE rats were markedly increased, while Bcl-2 levels(0.27±0.01 vs. 0.57±0.02)were decreased(all P<0.05). Compared to the SE group, low, medium and high doses Glycyrrhizin could effectively reduce the levels of Bax(0.51±0.02, 0.45±0.03 and 0.40±0.02 vs. 0.57±0.01)and Caspase-3(0.47±0.02, 0.42±0.02 and 0.37±0.01 vs. 0.54±0.00), and increase the levels of Bcl-2(0.41±0.02, 0.45±0.02 and 0.51±0.01 vs. 0.27±0.01)(all P<0.05). Conclusions:Glycyrrhizin can effectively protect the hippocampus of young rats with SE.
ABSTRACT
Objective:To study the protective effects of various doses of Glycyrrhizin on hippocampus of young rats with status epilepticus (SE).Methods:Lithium chloride and pilocarpine were injected intraperitoneally into male Sprague-Dawley (SD) rats (with a postnatal age of 18-21 days), so as to induce SE in rats.The rats were divided into 5 groups according to the random number table method: control group, SE group, SE+ low dose Glycyrrhizin group, SE+ medium dose Glycyrrhizin group and SE+ high dose Glycyrrhizin group.Three different doses of Glycyrrhizin (20 mg/kg, 40 mg/kg and 60 mg/kg) were injected intraperitoneally into the rats.The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in serum of SE rats were determined by enzyme linked immunosorbent assay.Quantitative real-time PCR (qRT-PCR) was used to detect the mRNA expression levels of TNF- α, IL-1β and IL-6 in hippocampus of SE rats.The expression levels of Bax, Bcl-2 and Caspase-3 in hippocampus were detected by Western blot.The damage of neurons was measured by hematoxylin and eosin (HE) staining and Nissl staining.Neurons apoptosis was examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The mitochondrial changes were observed under transmission electron microscopy.One-way ANOVA followed by Tukey post-hoc test was used for statistical analysis. Results:Compared to the control group, TNF-α[(369.69±58.07) ng/L vs. (75.46±14.64) ng/L], IL-1β[(242.27±25.23) ng/L vs. (45.29±5.90) ng/L] and IL-6[(288.15±24.60) ng/L vs. (46.59±8.80) ng/L] in the serum of SE rats were significantly up-regulated(all P<0.05). Compared to SE group, low, medium and high doses Glycyrrhizin could effectively reduce the levels of TNF-α[(216.67±8.31) ng/L, (158.81±5.03) ng/L and (113.69±12.54) ng/L vs. (369.69±58.07) ng/L], IL-1β[(131.21±5.50) ng/L, (86.60±7.79) ng/L and (65.06±4.39) ng/L vs. (242.27±25.23) ng/L] and IL-6[(150.24±9.48) ng/L, (101.70±5.85) ng/L and (91.60±2.81) ng/L vs. (288.15±24.60) ng/L] released in serum after SE occurred (all P<0.05). The neuronal damage, loss, apoptosis and mitochondrial damage were found in the hippocampus of SE rats.Glycyrrhizin could ameliorate these symptoms.Compared to the control group, Bax levels(0.57±0.01 vs. 0.14±0.01)and Caspase-3 levels(0.54±0.00 vs. 0.11±0.01)in the hippocampus of SE rats were markedly increased, while Bcl-2 levels(0.27±0.01 vs. 0.57±0.02)were decreased(all P<0.05). Compared to the SE group, low, medium and high doses Glycyrrhizin could effectively reduce the levels of Bax(0.51±0.02, 0.45±0.03 and 0.40±0.02 vs. 0.57±0.01)and Caspase-3(0.47±0.02, 0.42±0.02 and 0.37±0.01 vs. 0.54±0.00), and increase the levels of Bcl-2(0.41±0.02, 0.45±0.02 and 0.51±0.01 vs. 0.27±0.01)(all P<0.05). Conclusions:Glycyrrhizin can effectively protect the hippocampus of young rats with SE.
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OBJECTIVE: To explore the effects of lead exposure on inflammatory damage of hippocampus and cognitive impairment in diabetic rats. METHODS: The specific pathogen free(SPF) male healthy Wistar rats were randomly divided into control group and lead-exposed group. The SPF male Goto-Kakisaki Wistar rats rats were randomly divided into diabetes group and diabetes lead-exposed group, with 10 rats in each group. Rats in lead-exposed group and diabetes lead-exposed group were continuously exposed to lead acetate water with a mass fraction of 0.025% for 9 weeks. Rats in control group and diabetes group were given distilled water. The body weight and blood glucose level of rats were measured before lead exposure and at 1, 3, 5, 7 and 9 weeks after exposure. After the exposure, Morris water maze test was used to evaluate the learning and memory ability of rats. The lead levels in whole blood and hippocampal tissues were detected by inductively coupled plasma mass spectrometry, and the expression of mRNA and protein expression of inflammatory factors in hippocampal tissues of rats were detected by real-time fluorescence quantitative polymerase chain reaction and enzyme-linked immunoadsorption, respectively. RESULTS: At the end of lead exposure, the difference of body mass of rats in the diabetes group and the diabetes lead-exposed group was not statistically significant compared with that in the same group before exposure(all P values were >0.05); but the body mass of rats in these two groups was lower than that of the control group and the lead-exposure group(all P values were <0.05). The blood glucose levels of rats were higher in the diabetic group and the diabetes lead-exposed group than that in the control group and the lead-exposed group, respectively(all P values were <0.05). Morris water maze test showed that the escape latency of rats in the 1 st, 2 nd and 3 rd day were longer in diabetes group and the diabetes lead-exposed group than that in the control group and the lead-exposed group(all P values were <0.05). The number of times of crossing platforms were less in the lead-exposed group and the diabetes group than that of the control group(all P values were <0.05). The number of times of crossing platforms was more in the diabetes lead-exposed group than that in the other 3 groups(all P values were <0.05). The levels of lead in blood and hippocampus of rats were higher in the lead-exposed group than those in the control group(all P values were <0.05), and those in the diabetes lead-exposed group were higher than that in the other 3 groups(all P values were <0.05). The relative expression of mRNA of interferon-γ(ifn-γ) and interleukin(il)-6 in hippocampal tissues of rats was higher in the lead-exposed group and the diabetes group than that of the control group(all P values were <0.05). The relative expression of mRNA of tumour necrosis factor-α(tnf-α) and il-1β in the hippocampal tissues of rats was higher in the diabetes group than that of the control group and the lead-exposed group, respectively(all P values were <0.05). The relative expression of mRNA of ifn-γ, tnf-α, il-1β and il-6 in hippocampal tissues of rats was higher in the diabetes lead-exposed group than that of the other 3 groups(all P values were <0.05). The relative protein expression of IFN-γ, TNF-α, IL-4 and IL-6 in hippocampal tissues of rats was higher in lead-exposed group than that of the control group(all P values were <0.05). The relative protein expression of IFN-γ, TNF-α, IL-1β and IL-6 in hippocampal tissues of rats was higher in diabetes group than that of the control group(all P values were <0.05). The relative protein expression of IFN-γ, IL-1β and IL-6 in hippocampal tissues of rats was higher in diabetes group than that of the other 3 groups(all P values were <0.05). CONCLUSION: Diabetes can promote the lead accumulation in the blood and hippocampus of rats. The combined effect of lead exposure and diabetes can up-regulate the expression of pro-inflammatory cytokines in the hippocampal tissues of rats, aggravate the inflammatory response, and have a synergistic effect on the cognitive impairment in rats.
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OBJECTIVE： To study the improving effects of echinacoside （ECH） on spatial cognitive function in mice under hypobaric hypoxia environment and its mechanism. METHODS： Totally 60 mice were randomly divided into blank group （normal saline）， model group （normal saline）， positive group （Ginkgo leaf extract tablet，100 mg/kg） and ECH low-dose， medium-dose and high-dose groups （50， 75， 100 mg/kg）， with 10 mice in each group. Except for blank group， other groups were cultured in hypobaric oxygen chamber to simulate hypobaric hypoxia； they were given relevant medicine intragastrically once a day， for consecutive 7 d （Placing into hypobaric oxygen chamber immediately after medication）. Using the times of horizontal and vertical activities of mice in 2 min as index， negative emotions and spatial cognitive function were evaluated. Histopathological changes of hippocampus in mice were observed by microscopy after HE staining. The levels of SOD， CAT， GSH-Px and MDA in hippocampal tissue of mice were detected. RESULTS： Compared with blank group， the times of horizontal activities， MDA level were increased significantly in model group （P＜0.05）， while the times of vertical activities， the levels of SOD， CAT and GSH-Px were decreased significantly （P＜0.05）； the pyramidal cells in the CA1 area of the hippocampal tissue were arranged loosely， and many pyramidal cells were compressed and stained deeply. Compared with model group， the times of horizontal activities and MDA level were decreased significantly in positive group and ECH high-dose group （P＜0.05）， while the times of vertical activities， the levels of SOD， CAT and GSH-Px were increased significantly （P＜0.05）； the pyramidal cells in the CA1 region of the hippocampal tissue were abundant and closely arranged， and a few of them are constricted and deeply stained. CONCLUSIONS： ECH can improve spatial cognitive impairment of mice under hypobaric hypoxia environment， the mechanism of which may be associated with up-regulation of SOD， CAT and GSH-Px， down-regulation of MDA in the hippocampal tissue.