The renin-angiotensin system plays an important role in the pathogenesis and chronic progress of renal diseases. The increased plasma level of angiotensin can induce the changes of haemodynamics and diverse cytokines secreted by the kidney, and the change promotes the renal injury. How to block renin-angiotensin system has been a focus of nephrology. Recently, with the emerging of angiotensin receptor antagonist, the relationship between the angiotensin receptor antagonist and renal diseases has being realized.

TRP(transient receptor potential) ion channel is a kind of membrane proteins which are widespreadly present in various cells,which is used to identify various mixed flavor and warm,heat,cold,and other temperature.Originally cloned as a proatate-specific protein.TRPM8 is now best known as a cold-and menthol-activated channel implicated in thermosensation.We provide a brief review of current knowledge concerning the biophysical properties,gating mechanisms,pharmacology and(patho)physiology of this TRP channel.

Objective To investigate the analgesic effect of a specific p38MAPK inhibitor SB203580 in a rat model of chronic constriction injury (CCI) to sciatic nerve. Methods Male SD rats weighing 220-250 g were used in this study. The neuropathic pain model was established by CCI to sciatic nerve. The rats were anesthetized with intraperitoneal (i.p.) pentobarbital 40 mg?kg-1. Left sciatic nerve was exposed and 4 loose ligatures were placed on left sciatic nerve at 1 mm intervals with 4-0 silk suture. The animals were allowed 7 days to recover from surgery. Intrathecal (IT) SB203S80 was given through a needle inserted at L5,6 interspace. In experiment A, 40 rats wee randomly divided into 5 groups (n = 8 each): control group and 4 SBgroups (SB203580 0.1, 0.5, 2.5 and 5.0 ?g were given respectively) . Response of the hindpaw to mechanical stimulation with von Frey filament (MWT) was measured before (T0,baseline) and at 0.5, 3, 6, 12 and 24 h (T1-5) after IT SB203580 injection. In experiment B, 36 animals were randomly divided into 6 groups (n = 6 each): (1) sham operation group; (2) CCI group; (3) DMSO group; (4) SB 0.1 ?g group; (5) SB 0.5 ?g group and (6) SB 5.0 ?g group. The animals were lulled at 6h after IT SB203580 administration and L5,6 lumbar segment of the spinal cord was removed for determination of pCREB expression in the dorsal horn by immuno-cytochemistry. Results The rats developed hyperalgesia after CCI and IT SB203580 administration significantly increased MWT in a dose dependent manner. The number of pCREB positive neurons in the L4,5 spinal dorsal horn was significantly increased after CCI. Interthecal administration of SB203580 0.5 or 5.0 ?g significantly inhibited the CCI-induced increase in pCREB expression. Conclusion Intrathecal administration of SB203580 can attenuate the hyperalgesia induced by CCI and inhibition of CREB phosphorylation in the spinal dorsal horn is involved in the mechanism.

Objective To investigate the clinical value of radiotherapy combing with super selective esophageal intra-arterial infusion chemotherapy in advanced esophageal carcinoma. Methods 38 cases with medial or late stage of esophageal carcinoma wererandomly divided into two groups,the one group was treated with radiotherapy as the sole measure of treatment,while the other group was treated with radiotherapy combing with super selective esophageal intra-arterial infusion chemotherapy. All the patients were followed up within 3 to 24 months. Results In the most cases,the clinical symptoms and X-ray findings were improved obviously after treatment. But the rate of grade Ⅰof radiography was different obviously between two groups after different treatments.Conclusion Radiotherapy combing with interventional chemotherapy can increase drug concentration locally and therefore, has a better drug effect. On the other hand, it candecrease toxic reaction and can also decrease tumor volume effectively. So it can be a effective stratagem to those cases of locally advancedesophageal carcinoma which have poor reaction or severe radiotherapy reaction to merely radiotherapy.

Objective To investigate the effects of a highly selective protein kinase A (PKA) inhibitor, H89, injected intrathecally (IT) on hyperalgesia and phosphorylation of cAMP element binding protein(pCREB) in the dorsal horn neurons of the spinal cord induced by chronic constriction injury (CCI) to the sciatic nerve.Methods Fifty-eight adult female SD rats weighing 230-270 g were used in this study. CCI was produced by 4 loose ligatures place on the sciatic nerve of right hind leg at 1 mm interspace with 3-0 silk suture. The experiment was carried out in two parts. In part Ⅰ 28 animals were randomized to receive H89 1 (group H1), 2 (group H2 ) or 4 nmol (group H4) or 10 ?l of DMSO (the solvent) 10mmol?L-1 (control group) intrathecally (IT) (n = 7 each) 7 days after surgery. The paw-withdrawal latency following mechanical (MWL) and thermal stimulation (TWL) were recorded before (baseline) and 15, 30 and 60 min after drug administration. In part Ⅱ 24 rats were randomized to receive H89 1, 2 or 4 nmol or 10 ?l of DMSO 10 mmol?L-1 IT as in part Ⅰ (group H1, H2, H4 and control group, n = 6 each) . Another 6 animals received 10 ?l of DMSO 10 mmol?L IT 7 days after sham operation. The animals were killed 30 min after drug administration and lumbar (L4.5) segment of spinal cord was removed for determination of pCREB expression in the dorsal horn neurons of spinal cord using immuno-histochemical technique. Results MWL and TWL were significantly increased after drug administration in group H2(at 15min) and group H4(at 15 and 30 min) as compared to the baseline values(P

Objective To investigate the effect of propofol on the response of spinal cord to pain stimulation induced by intraplantar injection of formalin Methods Thirty SD rats of both sexes weighing 200 250g were randomly divided into six groups Pain stimulation was produced by subcutaneous injection of formalin (2 5%100?l) into the plantar region of unilateral front paw Group F received intraplantar injection of formalin only (n=6);group FP received intraperitoneal propofol 100?g?kg -1 10min after formalin injection (n=6); group PF received formalin injection 10min after intraperitoneal propofol 100?g?kg -1 (n=6); group P received intraperitoneal propofol 100?g?kg -1 only; group FS received intraperitoneal normal saline 10ml?kg -1 10min after formalin injection; and group S received intraperitoneal normal saline 10ml?kg -1 only 1 h after last injection (intraperitoneal or intraplantar) the animals were anesthetized and cervical spinal cord (where sensory nerves from front paw enter) was removed and sliced and examined for fos expression in the spinal cord using fos immunohistochemistry technique Results After formalin injection large numbers of fos like immunoreactive neurons (FLINs) were found in the ipsilateral dorsal horn Most of FLINs were confined to the medial part of outer area of laminal I and II Intraperitoneal propofol injected either before or after formalin stimulation significantly suppressed fos expression in all laminal (P

Objective To investigate the changes in acetylation of histone in the spinal dorsal horn in a rat model of persistent postoperative pain.Methods Ninety-six malc Sprague-Dawley rats,weighing 200-250 g,aged 6-8 weeks,were randomly divided into 2 groups (n=48 each) using a random number table:sham operation group (group S) and persistent postoperative pain group (group PPP).The rat model of persistent postoperative pain evoked by skin/muscle incision and retraction was established according to the method described by Flatters.After the rats were anesthetized with intraperitoneal chloral hydrate,the skin and superficial muscle of the medial thigh were incised and retractors inserted.This tissue was retracted for 1 h.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before operation and 1,3,7,14,and 21 days after operation.Four animals were sacrificed in each group after measurement of MWT at each time point for detection of acetylated histone H3 (Ac-H3) and acetylated histone H4 (Ac-H4) expression (by Western blot analysis) and the number of Ac-H3 and Ac-H4 positive cells in the spinal cord horn (by immunofluorescence histochemistry).Results Compared with group S,the MWT was significantly decreased at 3,7,14 and 21 days after operation,the expression of Ac-H3 and Ac-H4b was significantly down-regulated at 3,7 and 14 days after operation,and the number of Ac-H3 and Ac-H4 positive cells was significantly decreased at 7,14 and 21 days after operation in group PPP (P＜0.05 or 0.01).The MWT,expression of Ac-H3 and Ac-H4b,and the number of Ac-H3 and Ac-H4 positive cells were significantly higher at 21 days after operation than at 14 days after operation in group PPP (P＜0.05).Conclusion Acetylation of histone in the spinal dorsal horn is decreased after operation,which may be involved in the development and maintenance of persistent postoperative pain in rats.

Aim To explore the role of KATP in the pa-raventricular nucleus in inflammatory pain. MethodsMale Sprague-Dawley rats,250~280 g, were randomly assigned into 5 groups ( each, n =6 ): Normal group, Saline group ( for control, subcutaneous injection of 100 μl of saline into the plantar surface of the left hindpaw) , CFA group ( subcutaneous injection of 100μl of complete freund's adjuvant into the plantar sur-face of the left hindpaw) , Vehicle group ( treated with dimethylsulfoxide), KATP selective agonist group(trea-ted with diaoxide) . Rats in each group were tested for TWL with radiant heat apparatus. Immunofluorescent technique was used to label KATP in PVN and c-Fos in lumber spinal cord. Three days after injected with CFA, a selective KATP agonist, diaoxide, was injected into one side of PVN to test its effect on inflammatory pain and c-Fos expression in lumber spinal cord. Re-sults ① Compared with pre-operation and saline group, rats showed significantly lower TWL on day 1, 3, 7 after injection of CFA;the numbers of KATP posi-tive cells were significantly lower; the numbers of c-Fos positive cells were significantly higher. ② Com-pared with those of vehicle group, TWL and the num-ber of c-Fos in lumber spinal cord were both signifi-cantly lower after injection of diaoxide into one side of PVN. Conclusion KATP in PVN is related to inflam-matory pain.

AIM: To observe and compare the improvement of glomerul- osclerosis in rats with 5/6 nephrectomy by valsartan and benazepril. METHODS: Thirty Sprague-Dawley male rats were selected and performed five-sixths nephrectomy to produce chronic renal failure model. Two weeks after the surgery, the rats were randomly divided into model group, valsartan group and benazepril group, and established a shame group serving as normal control. The weight, blood pressure, blood uria nitrogen (BUN) and serum creatinine were measured on the sixth week after operation, then the rats were killed to take the kidneys for pathological histological observation. Immunohistochemistry was used to examine the expression of TGF-? 1 protein and fibronectin (FN) and collagen IV in glomeruli. RESULTS: As compared with model group, systolic pressure decreased (P

Objective To evaluate the effects of hydrogen-rich saline on chronic inflammatory pain in rats.Methods Thirty-two male Sprague-Dawley rats,aged 8-10 weeks,weighing 200-250 g,were randomly divided into 4 groups (n =8 each) using a random number table:control group (group C);complete Freund's adjuvant (CFA) group;hydrogen-rich saline group (group H2);CFA + hydrogenrich saline group (CFA+H2 group).Chronic inflammatory pain was induced by injecting CFA 100 μl into the plantar surface of the left hindpaw in CFA and CFA + H2 groups.In H2 and CFA + H2 groups,0.6 mmol/L hydrogen-rich saline 5 ml/kg was injected intraperitoneally once a day for 7 consecutive days starting from 1 day after injection of CFA,while the equal volume of normal salinc was given instead of hydrogen-rich saline in C and CFA groups.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before CFA injection and 1,3 and 7 days after CFA injection.The rats were sacrificed after the last measurement of pain threshold on day 7 after CFA injection.The left lumbar segments (L4 5) of the spinal cord were removed for determination of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression by Western blot.Results Compared with C group,no significant change was found in the MWT,TWL and expression of Nrf2 and HO-1 in H2 group,and the MWT was significantly decreased,the TWL was shortened,and the expression of Nrf2 and HO-1 was up-regulated in CFA and CFA+H2 groups.Compared with CFA group,the MWT was significantly increased,the TWL was prolonged,and the expression of Nrf2 and HO-1 was up-regulated in CFA+H2 group.Conclusion Hydrogen-rich saline can alleviate chronic inflammatory pain in rats,and activation of Nrf2/ARE signaling pathway in the spinal cord is involved in the mechanism.