Pramipexole attenuates 6-OHDA-induced Parkinson's disease by mediating the Nurr1/NF-κB pathway.

Neuroinflammation is the key factor associated with the progression of Parkinson's disease (PD). Pramipexole (PPX) has anti-inflammatory and antioxidant properties. This study explored the effects of PPX on PD and its related mechanisms. A PD rat model was established using 6-hydroxydopamine (6-OHDA). Thirty rats were divided into the following three groups: control, PD, and PD + PPX. The rats in the PD and PD + PPX groups were first administered 6-OHDA and then respectively treated with saline and PPX. Afterward, rotational behavior tests were performed to evaluate the efficiency of PPX. The level of tyrosine hydroxylase (TH) was measured using immunohistochemical staining. Subsequently, real-time quantitative PCR (RT-qPCR) and western blot were used to determine the expression of α-synuclein (α-syn), nuclear receptor subfamily 4 group A member 2 (Nurr1), and nuclear factor kappa B (NF-κB). PPX improved the motor behavior of PD rats caused by 6-OHDA. The number of TH-positive neurons in the PD group was significantly lower than that in the control group (P < 0.05), while PPX could rescue 6-OHDA-induced TH loss. RT-qPCR and western blot showed that Nurr1 expression was significantly downregulated in the PD group compared to that of the control group (P < 0.05), while after PPX treatment, its expression was significantly upregulated (P < 0.05). For α-syn and NF-κB, 6-OHDA significantly upregulated their expressions (P < 0.05), whereas PPX reversed them. PPX improved the motor behavior of PD through mediating the inflammatory response and regulating the Nurr1/NF-κB signaling pathway.

The association of lipid metabolism relative gene polymorphisms and ischemic stroke in Han and Uighur population of Xinjiang.

BACKGROUND: The present study is aimed to evaluate difference of lipid metabolism related gene single nucleotide polymorphisms (SNPs) with ischemic stroke (IS) in Han and Uighur population of Xinjiang, China. METHODS: Four hundred eight patients with ischemic stroke and 347 unrelated healthy individuals of age and sex matched were genotyped for Apolipoprotein A5 (ApoA5), lipoprotein lipase (LPL), Cholesteryl ester transfer protein (CETP) and low-density lipoprotein receptor (LDL-R) genes. Their mutation difference was analyzed by SNaP shot techniques. GeneMapper4.1 SPSS20.0 software was used for data management and analysis. Using a single locus analysis, the distribution difference of genotype loci in ischemic stroke cases and controls were detected to assess the genetic risk factors of ischemic stroke. RESULTS: Significance differences of genotype distribution in ischemic stroke cases and controls were observed in LDLR rs688 in Han and Uighur population in recessive model from analysis of single gene locus. It also was found that dramatic difference of triglyceride (TG) of LPL rs328 and systolic blood pressure in CETP rs708277 of total population. In binary logistic regression analysis of total studied population, ischemic stroke was observed significantly associated with LDLR rs688 both addictive model (TT/CC, adjusted OR = 1.47, 95% CI = 1.04-2.07) and recessive model (TT/CT + CC, adjusted Odds ratio (OR) = 2.66, 95% Confidence Interval (CI) = 1.37-5.14). In Han population, ischemic stroke was observed significantly associated with rs688 both in addictive model (TT/CC, adjusted OR = 3.27, 95% CI = 1.06-10.05). In Uighur population, no significant association was found between gene polymorphisms and the risk of ischemic stroke. Combined analysis of multiple gene and loci, interaction effects of LDLR rs688 C/T, ApoA5 rs662799 A/G and CETP rs708272 C/T denoted a significant influence on IS susceptibility. CONCLUSION: Single nucleotide polymorphisms of lipid metabolism relative gene were significantly associated with the morbidity of ischemic stroke in Han population. The interaction effects of rs688 C/T with ApoA5 rs662799 A/G and CETP rs708272 C/T promoted the occurrence of IS.

Gene Polymorphisms Affect the Effectiveness of Atorvastatin in Treating Ischemic Stroke Patients.

BACKGROUND/AIMS: The aim of the present study is to investigate whether the single nucleotide polymorphism (SNP) in lipid metabolism related genes would affect the effectiveness of atorvastatin in both Han and Uighur populations. METHODS: 200 ischemic stroke patients were treated with atorvastatin. The differences of blood lipid level and their ratios were measured. Six lipid related genes, HMGCR, APOA5, LPL, CETP, LDLR and PCSK9 were selected as candidate genes. And nine SNP loci in these six genes were genotyped by SNaPshot technique. RESULTS: In all patients treated with atorvastatin, the SNP rs662799 significantly affected the ratio of x0394;LDL and x0394;LDL/LDL (p < 0.05); the SNP rs320 significantly affected the ratio of x0394;LDL/LDL and x0394;(LDL/HDL)/(LDL/HDL) (p < 0.01) and the SNP rs708272 significantly affected the ratio of x0394;LDL (p < 0.05). In Han population treated with atorvastatin, the SNP rs662799 significantly affected the ratio of x0394;TG (p < 0.05); the SNP rs320 significantly affected the ratio of x0394;LDL/LDL and x0394;(LDL/HDL)/(LDL/HDL) (p < 0.01). In Uighur population treated with atorvastatin, the SNP rs2266788 significantly affected the ratio of x0394;HDL (p < 0.05); the SNP rs662799 significantly affected the ratio of x0394;LDL/LDL (p < 0.05) and the SNP rs708272 significantly affected the ratio of x0394;LDL (p < 0.05). CONCLUSION: Polymorphisms of rs662799 and rs2266788 in APOA5 gene, rs320 in LPL gene and rs708272 in CETP gene had significant association with the effect of the lipid-lowering therapy via atorvastatin calcium on ischemic stroke patients.

The association of serum lipid level with ischemic stroke in the elderly of Xinjiang.

BACKGROUND: The aim of the present study is to determine the association of serum lipid level in the above 55-year-old age elderly with ischemic stroke (IS) in Xinjiang regions, China. METHODS: 408 patients with IS and 347 healthy individuals as control in the ≥55-year-old elderly were selected for the present study in Xinjiang province of China from July 2010 to July 2012. Patients were divided into different groups according to the IS subtypes (large-artery atherosclerosis, LAA; cardio-aortic embolism CE; small-artery occlusion, SAO), plague stability, hypertension and diabetes. The serum lipid level including total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), Lipoprotein(a) (Lp(a)) and their ratios(TC/HDL, LDL/HDL, ApoA1/ApoB) were measured. RESULTS: Patients in LAA group had higher ratio of TC/HDL, ApoA1/ApoB and lower level of ApoA1 than SAO group(p<0.05); higher level of TC, HDL, LDL, TC/HDL, LDL/HDL, ApoA1/ApoB and lower level of ApoB compared with CE group. Patients in SAO group had higher level of LDL, ApoA1, ApoB, TC/HDL, LDL/HDL and ApoA1/ApoB than CE group. Patients with stable plaque had higher level of HDL and low level of LDL, ApoB, Lp(a), TC/HDL, LDL/HDL and ApoA1/ApoB than unstable plaque group. Patients with hypertension had higher level of TG, ApoB, Lp(a), LDL/HDL and ApoA1/ApoB than non-hypertensive group. Patients with diabetes had higher level of TC, TG, ApoB, TC/HDL, LDL/HDL, ApoA1/ApoB and low level of ApoA1 than non-diabetic group. Multiple logistic regression analysis revealed that high LDL, ApoB, LDL/HDL and ApoA1/ApoB might be the risk factors for ischemic stroke. CONCLUSION: An abnormal serum lipid level of the patients with IS in older Xinjiang population is significantly associated with the stroke subtypes, plaque stability, hypertension and diabetes.