AIM To study in vitro stereoselective metabolism of mandelic acid (MA) in 3 kinds of laboratory animal tissue fractions and observe the differences of MA biotransformation. METHODS MA enantiomers were incubated with the tissue fractions from rats, mice and rabbits. The phenylglyoxylic acid (PGA) concentrations in incubation mixture were determined by high-performance liquid chromatography. Coenzymes and inhibitors were co-incubated with MA to investigate their effects on MA metabolism. RESULTS Only S-MA showed a unique metabolism in liver and kidneys S9 fractions of rats. No inhibition of the enzyme activity was observed by addition of ethanol or 4-methyl pyrazole. NADPH caused a remarkable increase in S-MA metabolism. CONCLUSION Nonmicrosomal enzymes in kidneys and liver except alcohol dehydrogenase are responsible for the stereoselective metabolism of MA in rats. The MA biotransformation is significantly different between rats and mice or rabbits.

Objective:To elucidate the effect of P2X4 signal axis on iron metabolism in the substantia nigra (SN) of male rats with Parkinson′s disease (PD) successfully induced by 6-hydroxydopamine (6-OHDA).Methods:A total of 120 male rats were randomly divided into control group, 6-OHDA group (PD group), P2X4-gene virus (P2X4-positive intervention, P2X4-PI) group, P2X4-gene unloaded virus (P2X4-negative control, P2X4-NC) group, P2X4-PI+6-OHDA group (inject P2X4 gene virus first, then 6-OHDA two weeks later) and P2X4-NC+6-OHDA group (inject no-load gene virus first, then two weeks later with 6-OHDA) using a completely random numbers method, with 20 rats in each group. Brain stereotactic instrument was used to inject the corresponding grouped drugs into the left SN of rats. A behavioral test was performed two weeks after the modeling was completed to select the qualified rat models, and the initiation and balance ability of each group of rats were further evaluated by a balance bar experiment. The brains of the qualified rat models were decapitated, and the brain tissue was taken away and preserved after related treatment. Immunofluorescence staining and Western blotting methods were used to detect the number of tyrosine hydroxylase (TH) positive dopaminergic neurons, and the expression levels of protein in P2X4 purinergic receptor (P2X4R), divalent metal-ion transporter-1 (DMT1) and ferroportin 1 (FPN1).Results:The results of immunofluorescence staining showed that the number of TH positive dopaminergic neurons in the left SN of the PD group (4 724.0±261.1, t=13.17, P<0.01) and the P2X4-NC+6-OHDA group (4 470.0±228.9, t=14.21, P<0.001) was significantly lower than that of the control group (7 942.0±461.6). The number of TH positive dopaminergic neurons of the P2X4-PI+6-OHDA group (2 493.0±371.6, t=8.092, P<0.01) was significantly lower than that of the P2X4-NC+6-OHDA group. The results of Western blotting suggested that compared with the control group (1.723±0.146, 1.369±0.107, 1.020±0.059), the expression of P2X4R, DMT1 was increased, whereas FPN1 was decreased in the left SN of the PD group (2.107±0.070, t=4.368, P<0.05; 1.733±0.117, t=4.245, P<0.05; 0.783±0.042, t=5.795, P<0.01) and the P2X4-NC+6-OHDA group (2.104±0.110, t=4.326; 1.737±0.073, t=4.291; 0.804±0.037, t=5.282; P<0.05). Compared with the P2X4-NC+6-OHDA group, the expression of P2X4R, DMT1 was increased and FPN1 was decreased in the left SN of the P2X4-PI+6-OHDA group (2.875±0.170, t=8.770; 2.845±0.180, t=12.92; 0.550±0.040, t=6.216; P<0.01). Conclusion:The overexpression of P2X4 gene can up-regulate the expression of DMT1 and down-regulate the expression of FPN1 in the SN, which leads to the deposition of iron in the SN of the midbrain, and then may cause damage to dopaminergic neurons, and finally has an effect on the occurrence and development of PD.

Objective To investigate the value of susceptibility weighted imaging (SWI) with T1ρimaging in staging of hepatic fibrosis(HF) in rabbits. Methods Eighty selected white rabbits from New Zealand were randomly divided into the HF group (n=60) and the control group (n=20). Rabbits in the HF group were injected subcutaneously with 50％CCl4 oil solution to establish HF model,and the normal control rabbits were injected with saline solution subcutaneously.The HF group(n=15) and control group(n=5) were randomly selected at the 4th, 5th, 6th and 10th week after injection, to undergo liver MR scan. The liver signal intensity (SI liver), the muscle signal intensity (SI muscle),liver-to-muscle SI ratios (SIR) and liver T1ρvalues were measured. Scheuer was adopted to stage the rabbits in HF. One-way analysis of variance was used to compare the differences between SIR and T1ρ values in different stages of HF pathological. Spearman correlation was used to analyze the correlation between SIR and T1ρ values in the different stage of HF pathological.The ROC were used to compare the efficacy between SIR and T1ρvalues in the diagnosis of HF pathological stage. Results Among the final qualified 68 rabbits in the study, 17 in F0 phase, 11 in F1 phase, 16 in F2 phase, 11 in F3 phase, and 13 in F4 phase. The SIR were (0.977 ± 0.013), (0.960 ± 0.015), (0.802 ± 0.026), (0.786 ± 0.022), (0.541 ± 0.116); T1ρ values were (22.301 ± 1.849), (24.034 ± 0.867), (25.374 ± 1.309),(25.364±1.945),(30.948±2.925) ms.There were statistically significant in SIR between F0 and F2,F0 and F3, F0 and F4, F1 and F2, F1 and F3, F1 and F4, F2 and F4, F3 and F4 (P<0.01). There were statistically significant in T1ρvalues between F0 and F1,F0 and F2,F0 and F3,F0 and F4,F1 and F2,F1 and F4,F2 and F4, F3 and F4(P<0.05). SIR were negatively correlated with HF staging while T1ρ values were positively. ROC showed that the AUC of the T1ρvalues was slightly larger than SIR in the F4 group(0.992>0.966),and the AUC of the SIR was greater than T1ρvalues in the other groups. Conclusion SWI and T1ρvalues can provide an important objective basis in staging of HF. Both of them have great clinical application prospects but SIR diagnostic efficiency is slightly better than that of T1ρvalues.