Captopril related kidney damage: renal afferent arteriolar responses to angiotensin II and inflammatory signaling / 生理学报

Captopril can have nephrotoxic effects, which are largely attributed to accumulated renin and "escaped" angiotensin II (Ang II). Here we test whether angiotensin converting enzyme-1 (ACE1) inhibition damages kidneys via alteration of renal afferent arteriolar responses to Ang II and inflammatory signaling. C57Bl/6 mice were given vehicle or captopril (60 mg/kg per day) for four weeks. Hypertension was obtained by minipump supplying Ang II (400 ng/kg per min) during the second 2 weeks. We assessed kidney histology by periodic acid-Schiff (PAS) and Masson staining, glomerular filtration rate (GFR) by FITC-labeled inulin clearance, and responses to Ang II assessed in afferent arterioles in vitro. Moreover, arteriolar H2O2 and catalase, plasma renin were assayed by commercial kits, and mRNAs of renin receptor, transforming growth factor-β (TGF-β) and cyclooxygenase-2 (COX-2) in the renal cortex, mRNAs of angiotensin receptor-1 (AT1R) and AT2R in the preglomerular arterioles were detected by RT-qPCR. The results showed that, compared to vehicle, mice given captopril showed lowered blood pressure, reduced GFR, increased plasma renin, renal interstitial fibrosis and tubular epithelial vacuolar degeneration, increased expression of mRNAs of renal TGF-β and COX-2, decreased production of H2O2 and increased catalase activity in preglomerular arterioles and enhanced afferent arteriolar Ang II contractions. The latter were blunted by incubation with H2O2. The mRNAs of renal microvascular AT1R and AT2R remained unaffected by captopril. Ang II-infused mice showed increased blood pressure and reduced afferent arteriolar Ang II responses. Administration of captopril to the Ang II-infused mice normalized blood pressure, but not arteriolar Ang II responses. We conclude that inhibition of ACE1 enhances renal microvascular reactivity to Ang II and may enhance important inflammatory pathways.

Effect of acupoint thread-embedding on macrophage polarization of epididymis adipose tissue in obese mice / 中国针灸

OBJECTIVE@#To observe the effect of acupoint thread-embedding at "Zusanli" (ST 36) and "Fenglong" (ST 40) on the macrophage polarization of epididymis adipose tissue in obese mice, and to explore the action mechanism of acupoint thread-embedding on weight control.@*METHODS@#Among 30 male C57BL/6 mice, 10 mice were randomly selected and fed with normal diet, and the remaining 20 mice were fed with high-fat diet to establish the obesity model. Sixteen mice with successful obesity model were randomly divided into a model group and an acupoint thread-embedding group, 8 mice in each group. Eight mice were selected from mice which were fed with normal diet as the normal group. On the next day of successful modeling, acupoint thread-embedding was performed at "Zusanli" (ST 36) and "Fenglong" (ST 40) in the acupoint thread-embedding group, once every 10 days for 4 times. The body weight was recorded at 0, 8, 16, 24, 32, 40 days into intervention; the level of glucose metabolism was compared after intervention; the level of lipid metabolism and weight of epididymal adipose tissue were compared at the end of the intervention; the mRNA expression of M1 and M2 macrophage-related cytokines interleukin-10 (IL-6), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were detected by real-time PCR; the mRNA and protein expression of M1 macrophage labeled inducible nitric oxide synthase (iNOS) and M2 macrophage labeled arginase-1 (Arg-1) were detected by real-time PCR and Western blot.@*RESULTS@#Compared with the normal group, the body weight at 0, 8, 16, 24, 32, 40 days into intervention in the model group was increased (@*CONCLUSION@#Acupoint thread-embedding at "Zusanli" (ST 36) and "Fenglong" (ST 40) may play a role in weight control by regulating the polarization of macrophages.

Effect of acupuncture on oxidative stress and apoptosis-related proteins in obese mice induced by high-fat diet / 中国针灸

OBJECTIVE@#To explore the effect of acupuncture on oxidative stress and apoptosis-related proteins of liver in obese mice induced by high-fat diet.@*METHODS@#A total of 45 male C57BL/6 mice were randomized into a control group (10 mice) and a model established group (35 mice). Mice in the model established group were fed with high-fat diet for 16 weeks to establish the obesity model. After model established, 30 mice were randomized into a model group, a non-acupoint group and an acupoint group, 10 mice in each one. Acupuncture was applied at "Guanyuan" (CV 4), " Zusanli" (ST 36), "Yishu" (EX-B 3) in the acupoint group and the points of 0.5 cm and 1 cm to the base of tail in the non-acupoint group, 15 min each time, once a day for 8 weeks. Mice in the control group were fed with normal diet, while mice in the other 3 groups were fed with high-fat diet continuously for 8 weeks. The body weight was measured at 0, 4th, 8th, 12th, 16th, 20th, 24th week in each group respectively. After 24-week intervention, the weight of white adipose tissue of epididymis and perirenal and liver was measured; the levels of serum alanine transaminase(ALT) and glutamic oxaloacetic aminotransferase (AST) were detected by automatic biochemical analyzer; liver homogenate was used to detect the level of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD); the liver morphology was observed by HE staining; the expression of apoptosis-related proteins Bax and Bcl-2 were detected by Western blot.@*RESULTS@#Compared with the control group, the body weight of mice in the model group, the acupoint group and the non-acupoint group was decreased on 16th week into experiment (before intervention, <0.05); compared with the model group and the non-acupoint group, the body weight of mice in the acupoint group were decreased after intervention (<0.05). Compared with the control group, the weight of white adipose tissue and liver, the levels of serum ALT and AST, the level of liver MDA, the expression of liver Bax were increased (<0.05); the activity of liver SOD and the expression of liver Bcl-2 were decreased in the model group after intervention (<0.05). Compared with the model group and the non-acupoint group, the weight of white adipose tissue and liver, the levels of serum ALT and AST, the level of liver MDA, the expression of liver Bax were decreased (<0.05); the activity of liver SOD and the expression of liver Bcl-2 were increased in the acupoint group after intervention (<0.05).@*CONCLUSION@#Acupuncture at "Guanyuan" (CV 4), "Zusanli" (ST 36) and "Yishu"(EX-B 3) can improve obesity and obesity related hepatic disorder by regulating oxidative stress and inhibiting apoptosis in liver.

Study of hypermethylation of SOCS gene in typical myeloproliferative disease / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical role of hypermethylation of suppressor of cytokine signaling (SOCS) on typical myeloproliferative disease (MPD) patients and its mechanism.</p><p><b>METHODS</b>Methylation specific PCR was used to detect SOCS1, 2, 3 methylation, direct DNA sequencing was performed to detect JAK2V617F mutation, real-time fluorescence quantitative PCR were applied to evaluate transcriptional activity of SOCS1, 2, 3.</p><p><b>RESULTS</b>Among 100 MPD patients, hypermethylation of SOCS1 was detected in 27 (27%), hypermethylation of SOCS2 in 9 (9%), hypermethylation of SOCS3 in 34 (34%); JAK2V617F mutation in 64 (64%). Hypermethylation of SOCS1, 3 greatly inhibited gene expression compared with unmethylated ones (P < 0.05). Presence of JAK2V617F mutation markedly down-regulated SOCS1, 3 gene mRNA expression compared with wild JAK2V617F (P < 0.05).</p><p><b>CONCLUSION</b>Hypermethylation of SOCS1, 3 and JAK2V617F mutation exist in MPD, which inhibited SOCS1, 3 gene expression. SOCS hypermethylation and JAK2V617F mutation can activate JAK-STAT signaling pathways, these observations may provide a potential therapeutic direction.</p>

Mental status of surgical medical staff who treated or did not treat the victims in Wenchuan earthquake / 中南大学学报(医学版)

OBJECTIVE@#To compare and analyze the mental status of medical staff between Orthopedics Department who treated the victims in the earthquake and other surgical departments who did not treat the victims in the earthquake, and to provide evidence for psychological prevention and intervention in the earthquake aids.@*METHODS@#Cross-sectional study was used to choose staff in the Orthopedics Department who treated the victims and other surgical departments who did not treat victims in the earthquake as eligible subject with convenient sampling. The research tool is Symptom Checklist-90. The questionnaire was done by participants with the same psychological instruction. Data were analyzed by SPSS16.0.@*RESULTS@#The scores in somatization, depression,anxiety and opposition, phobic anxiety in the orthopedic staff were significantly higher than those of the other surgical staff (P < 0.05).@*CONCLUSION@#There is disorder in mental health of medical staff in Orthopedics Department and mental intervention is needed.

Effects of electroacupuncture on GDNF positive cell immunoreactivity in local dermal tissue of the inflammatory pain focus in the rat of adjuvant arthritis / 中国针灸

<p><b>OBJECTIVE</b>To study on the analgesic mechanism of electroacupuncture (EA) in the rat of adjuvant arthritis (AA).</p><p><b>METHODS</b>Forty-eight SD rats were randomly divided into a blank control group (n = 8), an inflammatory group (n = 10), an acupoint EA group (n = 10), a non-acupoint EA group (n = 10) and a contralateral acupoint EA group (n = 10). Complete Freund's adjuvant (CFA) 50 microL were injected into the left malleolus' articular cavity in the rats except the blank control group for preparing single local adjuvant arthritis (AA) model. EA was given every other day to the acupoint EA group, the non-acupoint EA group and the contralateral acupoint EA group. The improving effects of EA at "Huantiao" (GB 30) and "Yanglingquan" (GB 34) on the dorsal flexion pain score and the swell of dorsum of hind paw were investigated, and effects of EA on Glial cell line-derived neurotrophic factor (GDNF) positive cells immunoreactivity in the inflammatory tissue of the AA rats on the 14th day after injection of adjuvant were observed with immunohistochemical technique.</p><p><b>RESULTS</b>Hyperalgesia and local swell, and GDNF in the dermal and subcutaneous tissue around the inflammatory ankle joint in the inflammatory groups were significantly higher than those in the blank control group. EA on the ipsilateral and contralateral acupoints reduced the pain, promoted the recovery of swell, and decreased the positive area percentage and mean optical density of GDNF positive cells in the dermal and the subcutaneous tissues. However, the non-acupoint EA group did not have this action.</p><p><b>CONCLUSION</b>EA can regulate expression of GDNF in local dermal tissue of the inflammatory focus in the AA rat, so as to exert the anti-inflammatory and analgesic effects.</p>