ABSTRACT
Objective:To investigate the effect of lappaconitine (LA) on neuropathic pain (NPP) mediated by retrograde transport of purinergic P2X3 receptor (P2X3R) in dorsal root ganglion (DRG) neurons of rats with chronic constriction injury (CCI) of the sciatic nerve.Methods:Seventy-two male healthy SD rats were selected to construct the NPP model following CCI of the sciatic nerve by ligating the right sciatic nerve. according to the random number table method. The rats were divided into CCI group, CCI+LA group and normal control group according to the random number table method, with 24 rats in each group. In normal control group, the right sciatic nerve was exposed without ligation. In CCI+LA group, the rats were given 2 g/L LA (ie, 4 mg/kg intravenously for once a day for one day only) after the same treatment as CCI group. Other two groups were injected with the identical amount of normal saline in the same way. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were evaluated before injury and at 2, 6, 12 and 24 hours after injury to evaluate the symptoms of neuralgia caused by nerve injury. The proximal and distal nerve fragments were collected in the three groups at 2, 6, 12 and 24 hours after injury. Western blotting was applied to analyze the expression of P2X3R at 2, 6, 12 and 24 hours after injury and the expression of neurotrophic factor (NGF) and tyrosine kinase receptor A (TrkA) at 24 hours after injury to evaluate the effect of LA on P2X3R, NGF and TrkA.Results:There were insignificant differences in MWT and TWL among all groups before injury (all P>0.05). Compared with normal control group, MWT and TWL were significantly decreased in CCI group and CCI+LA group at 2, 6, 12 and 24 hours after injury (all P<0.05 or 0.01). There were insignificant differences in MWT and TWL between CCI group and CCI+LA group at 2 and 6 hours after injury (all P>0.05), while MWT and TWL were significantly higher in CCI+LA group than those in CCI group at 12 and 24 hours after injury (all P<0.05 or 0.01). In the proximal sciatic nerve segment, Western blotting showed similar levels of P2X3R among all groups at 2, 6, 12 and 24 hours after injury (all P>0.05). In the distal sciatic nerve segment, Western blotting showed higher expression of P2X3R in CCI group than that in normal control group at 2, 6, 12, 24 hours after injury (all P<0.01), higher expression of P2X3R in CCI+LA group than that in normal control group at 2, 6 and 12 hours after injury (all P<0.05), similar expression of P2X3R expression between CCI+LA group and normal control group at 24 hours after injury ( P>0.05), similar expression of P2X3R between CCI group and CCI+LA group at 2 and 6 hours after injury (all P>0.05), and lower expression of P2X3R in CCI+LA group than that in CCI group at 12 and 24 hours after injury ( P<0.05 or 0.01). In the proximal and distal nerve fragments, the expression of NGF was lower in normal control group than that in CCI group and CCI+LA group ( P<0.05 or 0.01), but was similar between CCI group and CCI+LA group at 24 hours after injury ( P>0.05). In the proximal and distal nerve fragments, there were insignificant differences in the expression of TrkA among all groups at 24 hours after injury (all P>0.05). Conclusion:Early LA treatment after injury can alleviate mechanical and thermal hyperalgesia in NPP rats, which may be related to the reduction of P2X3R retrograde transport in DRG neuron axonal.
ABSTRACT
Objective To explore the correlation of high-sensitivity C-reactive protein (hs-CRP) with risk factors and target organ damage in hypertensive patients.Methods The levels of serum hs-CRP of 216 hypertensive cases (hypertension group) and 36 healthy subjects (control group) were tested and compared among different associated diseases, the number of involved target organ and the difference of involved target organ.The relativity between variables such as total cholesterol, high density lipoprotein cholesterol (HDL-C), left ventricular mass index (LVMI) and so on and hs-CRP was analyzed by linear correlation analysis and multiple linear regression analysis.Results The levels of serum hs-CRP in hypertension group were higher than those in control group[( 1.99 ± 0.34) mg/L vs.( 1.10 ± 0.26 ) mg/L](P ＜ 0.01 ).The levels of serum hs-CRP in hypertension combined with coronarv disease and hvoertension combined with diabetes mellitus[(2.39 ± 0.24), (2.10 ± 0.18 ) mg/L, respectively]were higher than those in simple hypertension[( 1.85 ± 0.30 ) mg/L], and the levels of serum hs-CRP in hypertension combined with coronary disease were higher than those in hypertension combined with diabetes mellitus, and there were significant difference (P ＜ 0.05 ).The levels of serum hs-CRP were positively correlated with the number of involved target organ (r =0.747,P ＜0.01 ).There were significant differences among different associated diseases.The levels of serum hs-CRP in hypertension combined with left ventricle thickening were higher than those in hypertension combined with carotid atherosclerosis, renal damage and diabetic retinopathy,and there were significant differences (P ＜ 0.05 ).There was no significant difference in the level of serum hs-CRP between hypertension combined with carotid atherosclerosis and hypertension combined with renal damage (P ＞ 0.05 ).Stepwise regression analysis showed that the dominating factors of the level of serum hs-CRP were LVMI, age and HDL-C, and the level of hs-CRP showed negative correlation with HDL-C.Conclusions The levels of serum hs-CRP in hypertensive patients are higher than those in healthy subjects.The more number of involved target organ, the higher levels of serum hs-CRP.Patients with different involved target organ have different inflammatory degree.The levels of serum hs-CRP in hypertension combined with coronary disease are higher than those in hypertension combined with diabetes mellitus.Stepwise regression analysis shows that the dominating factors for hs-CRP levels are LVMI, HDL-C and age.