1.Study on Anti-inflammatory Effect and Mechanism of Jingulian Capsule on Inflammatory Model Rats
Zhili FU ; Jian PU ; Gonglu LI ; Dan TAN ; Lin ZHENG ; Yongjun LI ; Yong HUANG
China Pharmacy 2021;32(9):1077-1082
OBJECTIVE:To study the anti- inflammatory effect and mechanism of Jingulian capsule on inflammatory model rats. METHODS :Totally 48 rats were randomly divided into blank control group ,model group ,Jingulian capsule low-dose , medium-dose and high-dose groups (0.66,1.32,2.64 g/kg),dexamethasone group (positive control ,0.945 mg/kg),with 8 rats in each group. Blank control group and model group were given constant volume of water intragastrically ,and other groups were given relevant medicine intragastrocally ,twice a day ,for consecutive 3 days. Thirty minutes after last administration ,model group and administration groups were given lipopolysaccharide (10 mg/kg)intraperitoneally to induce inflammatory model. Six hours after intraperitoneal injection ,the contents of TNF-α,IL-1β,IL-6,PGE2 in serum were detected by ELISA. The wet to dry weight (W/D)ratio of lung tissue were determined. HE staining was used to observe the pathological changes of lung tissue . RT-PCR was used to detect the mRNA expression of TNF-α,IL-6,PGE2 and IL- 1β in lung tissue. Western blot assay was used to detect the phosphorylation of NF-κB p65 protein and the expression of IκBα protein in lung tissue. RESULTS:Compared with blank ; control group ,the contents of TNF-α,IL-1β,IL-6 and PGE 2 in serum ,the W/D ratio of lung tissue ,the expression of TNF-α,IL-1β,IL-6 and PGE 2 mRNA and the phosphorylation level of NF-κB p65 protein in lung tissue of model group weresignificantly increased ,and the expression of IκBα proteinwas significantly decreased (P<0.05 or P<0.01);a large number of alveolar atrophy and collapse ,alveolar wall thickening ,lung consolidation ,and a large number of inflammatory cell infiltration could be seen in lung tissue. Compared with model group ,the contents of TNF-α,IL-1β(except for low-dose group ), IL-6 and PGE 2 in serum ,as well as the expression of TNF-α(except for high-dose group ),IL-1β,IL-6(except for low-dose , high-dose groups )and PGE 2 mRNA in lung tissue were decreased significantly in Jingulian capsule groups (P<0.05 or P<0.01); the W/D ratio of lung tissue was decreased significantly in Jingulian high-dose group (P<0.05 or P<0.01);the expression of phosphorylation level of NF-κB p65 protein in lung tissue of Jingulian medium-dose group were decreased significantly (P<0.05 or P<0.01),while the expression of IκBα protein was increased significantly(P<0.05);the alveolar structure was clear ,the alveolar wall was slightly thickened , and a small amount of inflammatory cell infiltration was seen in lung tissue. CONCLUSIONS:Jingulian capsule has good anti-inflammatory effect on inflammatory model rats ,the mechanism of which may be related to the inhibition of NF-κB signal pathway.
2.Penetrance estimation of PRRT2 variants in paroxysmal kinesigenic dyskinesia and infantile convulsions.
Yulan CHEN ; Dianfu CHEN ; Shaoyun ZHAO ; Gonglu LIU ; Hongfu LI ; Zhi-Ying WU
Frontiers of Medicine 2021;15(6):877-886
Proline-rich transmembrane protein 2 (PRRT2) is the leading cause of paroxysmal kinesigenic dyskinesia (PKD), benign familial infantile epilepsy (BFIE), and infantile convulsions with choreoathetosis (ICCA). Reduced penetrance of PRRT2 has been observed in previous studies, whereas the exact penetrance has not been evaluated well. The objective of this study was to estimate the penetrance of PRRT2 and determine its influencing factors. We screened 222 PKD index patients and their available relatives, identified 39 families with pathogenic or likely pathogenic (P/LP) PRRT2 variants via Sanger sequencing, and obtained 184 PKD/BFIE/ICCA families with P/LP PRRT2 variants from the literature. Penetrance was estimated as the proportion of affected variant carriers. PRRT2 penetrance estimate was 77.6% (95% confidence interval (CI) 74.5%-80.7%) in relatives and 74.5% (95% CI 70.2%-78.8%) in obligate carriers. In addition, we first observed that penetrance was higher in truncated than in non-truncated variants (75.8% versus 50.0%, P = 0.01), higher in Asian than in Caucasian carriers (81.5% versus 68.5%, P = 0.004), and exhibited no difference in gender or parental transmission. Our results are meaningful for genetic counseling, implying that approximately three-quarters of PRRT2 variant carriers will develop PRRT2-related disorders, with patients from Asia or carrying truncated variants at a higher risk.
Dystonia
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Epilepsy, Benign Neonatal/genetics*
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Humans
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Membrane Proteins/genetics*
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Mutation
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Nerve Tissue Proteins/genetics*
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Pedigree
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Penetrance
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Seizures/genetics*