Objective To investigate the effects of perampanel on the C-C chemokine receptor 5(CCR5)/cAMP-dependent protein kinase A(PKA)/cyclic-AMP response binding protein(CREB)pathway and hippocampal neuronal damage in epileptic rats.Methods Seventy-two male SPF-grade SD rats were randomly divided into epilepsy group,perampanel group,CCR5 inhibitor(maraviroc)group,recombinant CCL5 protein(rCCL5,CCR5 activator)group,perampanel+rCCL5 group,and a control group,with 12 rats in each group.The duration and frequency of epi-leptic seizures were detected in above groups.HE staining was used to observe the morphology of the hippocampal CA1 region.ELISA was employed to measure the contents of cyclooxygenase-2(COX-2),TNF-α,and IL-18 in the hippocampal CA1 region.Western blotting was conducted to measure the expression levels of CCR5,PKA,and p-CREB in the hippocampal CA1 region.Results Compared with the control group,the epilepsy group demonstrated badly-arranged and swollen neurons in the hippocampal CA1 region,longer duration of epilepsy,higher seizure frequency,increased COX-2,TNF-α and IL-18 contents in the CA1 region,elevated apoptotic rate and CCR5 protein level,and prolonged escape latency,while less number of crossing platforms and reduced protein levels of PKA and p-CREB(P＜0.05).While,both perampanel and maraviroc treatment could reverse above indicators when compared with the levels of the epilepsy group(P＜0.05).In the rCCL5 group,the neural injury was significantly aggravated,the duration of epilepsy and the frequency of epileptic seizures were increased,the contents of COX-2,TNF-α and IL-18 in the hip-pocampal CA1 region were enhanced,the rate of neuronal apoptosis and the expression of CCR5 protein were significantly enhanced,the escape latency was prolonged,and the number of crossed platforms,PKA,and the expression of p-CREb protein were declined(P＜0.05).When compared with the perampanel group,addition of rCCL5 resulted prolonged duration of epilepsy and escape latency,increased frequency of epileptic seizures and protein levels of COX-2,TNF-α,IL-18 and CCR5,more severe neuronal injury in the CA1 region,less platforms crossed,and decreased pro-tein expression of PKA and p-Creb(P＜0.05).The neural apoptotic rate in the hippocampal CA1 region was significantly higher in the perampanel+rCCL5 group than the perampanel group[(10.58±0.43)％vs(6.36±0.31)％,P＜0.05].Conclusion Perampanel may inhibit neuroin-flammation and neuronal apoptosis in epileptic rats by down-regulating CCR5 and then activating the PKA/CREB pathway,and thus attenuate hippocampal neuronal damage.

Objective To investigate the effects of perampanel on the C-C chemokine receptor 5(CCR5)/cAMP-dependent protein kinase A(PKA)/cyclic-AMP response binding protein(CREB)pathway and hippocampal neuronal damage in epileptic rats.Methods Seventy-two male SPF-grade SD rats were randomly divided into epilepsy group,perampanel group,CCR5 inhibitor(maraviroc)group,recombinant CCL5 protein(rCCL5,CCR5 activator)group,perampanel+rCCL5 group,and a control group,with 12 rats in each group.The duration and frequency of epi-leptic seizures were detected in above groups.HE staining was used to observe the morphology of the hippocampal CA1 region.ELISA was employed to measure the contents of cyclooxygenase-2(COX-2),TNF-α,and IL-18 in the hippocampal CA1 region.Western blotting was conducted to measure the expression levels of CCR5,PKA,and p-CREB in the hippocampal CA1 region.Results Compared with the control group,the epilepsy group demonstrated badly-arranged and swollen neurons in the hippocampal CA1 region,longer duration of epilepsy,higher seizure frequency,increased COX-2,TNF-α and IL-18 contents in the CA1 region,elevated apoptotic rate and CCR5 protein level,and prolonged escape latency,while less number of crossing platforms and reduced protein levels of PKA and p-CREB(P＜0.05).While,both perampanel and maraviroc treatment could reverse above indicators when compared with the levels of the epilepsy group(P＜0.05).In the rCCL5 group,the neural injury was significantly aggravated,the duration of epilepsy and the frequency of epileptic seizures were increased,the contents of COX-2,TNF-α and IL-18 in the hip-pocampal CA1 region were enhanced,the rate of neuronal apoptosis and the expression of CCR5 protein were significantly enhanced,the escape latency was prolonged,and the number of crossed platforms,PKA,and the expression of p-CREb protein were declined(P＜0.05).When compared with the perampanel group,addition of rCCL5 resulted prolonged duration of epilepsy and escape latency,increased frequency of epileptic seizures and protein levels of COX-2,TNF-α,IL-18 and CCR5,more severe neuronal injury in the CA1 region,less platforms crossed,and decreased pro-tein expression of PKA and p-Creb(P＜0.05).The neural apoptotic rate in the hippocampal CA1 region was significantly higher in the perampanel+rCCL5 group than the perampanel group[(10.58±0.43)％vs(6.36±0.31)％,P＜0.05].Conclusion Perampanel may inhibit neuroin-flammation and neuronal apoptosis in epileptic rats by down-regulating CCR5 and then activating the PKA/CREB pathway,and thus attenuate hippocampal neuronal damage.

Phytosterolemia is a rare, severe autosomal recessive sterol storage disorder caused by homozygous or compound heterozygous mutations in one of the ABCG5 and/or ABCG8 adenosine triphosphate binding cassette (ABC) genes. The most prominent features of phytosterolemia are the significantly increased serum content of plant sterols. Present review focused on the laboratory diagnosis of phytosterolemia, briefly described the metabolism of phytosterols, and introduced the latest research progress on phytosterolemia diagnosis, its relationship with ASCVD and laboratory diagnostic methods (including the detection of serum concentrations of phytosterols, ABCG5/G8 gene mutation). We hope this article could improve readers′ awareness and attention on this disease.

Objective To observe the vasodilation effect of extract of Jasminum samba (EJs), a kind of traditional Chinese medicine, on ex vivo rat thoracic aortic rings, and to investigate its mechanism. Methods On ex vivo aortic ring perfusion device, influence of EJs on contraction of the aorta induced by phenylephrine (PE) or potassium chloride (KCl) was observed. Influence of N-nitro-L-arginine-methylester ( L-NAME ), barium chloride ( BaCl2 ), glibenclamide ( Gli ) on vasodilating effect of EJs (0. 5, 1, 2, 4, 8 g·L-1 ) was detected. Effect of EJs on the contraction of calcium chloride (CaCl2 ) and PE in Ca2+-free medium was detected. [ Ca2+ ] i in vascular smooth muscle cells was determined by using laser scanning confocal microscope (LSCM). Results In blood vessels with intact endothelium, EJs concentration-dependently decreased PE- or KCl-induced vasoconstriction, the maximum dilating effect being (105. 0±3. 2)% and (78. 0±6. 5)% , respectively; L-NAME affected the vasodilatory effect of EJs on thoracic aorta rings ( P<0. 01), the maximum dilatory effect being (58. 0 ± 6. 9)% . BaCl2 and Gli had significant influence on vasodilation of EJs, and the contraction was obviously attenuated (P<0. 01), the maximum dilatory effect being (37. 0±5. 2)% and (78. 0±10. 0)% , respectively. EJs significantly inhibited contracting effect of PE on thoracic aorta rings in Ca2+-free medium (P<0. 01). The maximum contraction effect was (70. 0±6. 3)% . EJs inhibited CaCl2-induced vasoconstriction (0. 5-8 mmol·L-1 ), and vasoconstriction was decreased by (65. 0±3. 2)% . LSCM recorded that Fmax / F0 of 4 and 8 g·L-1 EJs was (2. 0±0. 2) and (1. 5±0. 2), respectively. Conclusion EJs exerted a dose-dependent vasodilating effect on rat isolated aorta rings. The mechanism might be related to promoting NO release, activating K+channels and decreasing the concentration of cytoplasmic Ca2+.