Rutin alleviates lupus nephritis by inhibiting T cell oxidative stress through PPARγ.

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by complex clinical symptoms and multi-organ damage. One of the most prevalent complications of SLE is lupus nephritis (LN). Rutin, a natural flavonoid compound found in various plants used in traditional Chinese medicine, has shown promising anti-inflammatory, antioxidant, and renal protective effects. In our study, we treated MRL/lpr mice, a model known for spontaneously developing LN, with Rutin. Our findings reveal that Rutin markedly reduced serum cytokine and autoantibody levels and decreased inflammatory cell infiltration in renal tissues, thereby ameliorating kidney pathology. In vitro experiments indicated that Rutin's therapeutic effect on LN is linked to its significant reduction of oxidative stress in T cells. Further investigations suggest that Rutin enhances oxidative stress management through the modulation of Peroxisome proliferator-activated receptor gamma (PPARγ). We observed that Rutin modulates PPARγ activity, leading to reduced transcriptional activity of NF-κB and STAT3, which in turn inhibits the secretion of inflammatory cytokines such as IL-6, TNF-α, and IL-17. In summary, Rutin can exert an antioxidant effect by regulating PPARγ and shows therapeutic action against LN.

Comparison of the Effects of Epidural Anesthesia and General Anesthesia on Perioperative Cognitive Function and Deep Vein Thrombosis in Patients Undergoing Total Knee Arthroplasty.

OBJECTIVE: To explore the effects of epidural anesthesia and general anesthesia on perioperative cognitive function and deep vein thrombosis (DVT) in patients undergoing total knee arthroplasty (TKA). METHODS: Total of 68 patients undergoing TKA in our hospital from September 2019 to March 2021 were selected and divided into the control group under general anesthesia and the observation group under epidural anesthesia according to the different anesthesia methods, 34 patients in each group. TKA was selected in both groups and performed by the same group of physicians, anesthesiologists, and nursing staff. The mean arterial pressure (MAP), heart rate (HR), and blood oxygen saturation (SpO2) were observed immediately before anesthesia (T1), 30 min after anesthesia (T2), after surgery (T3), and 1 d after surgery (T4). The changes of platelet (PLC), fibrinogen (Fbg), prothrombin time (PT), activated partial thrombin time (APTT), and other coagulation indicators were recorded. The Montreal Cognitive Assessment (MoCA) scores before surgery and 1 d and 3 d after surgery were observed. The blood samples of the two groups were collected before surgery and 1 d and 3 d after surgery, and the levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the peripheral blood of the two groups were measured by ELISA. The number of postoperative mental disorders and DVT in the two groups was calculated. RESULTS: The MAP and HR of T4 were lower than those of T1, T2, and T3. The MAP of T2, T3, and T4 in the observation group was lower than that in the control group (P < 0.05), and the SpO2 of T1-T4 in the two groups did not change significantly, and there was no significant difference between the two groups (P > 0.05). Compared with T1, there was no significant difference in PLC, Fbg, and PT in the observation group T4 (P > 0.05), and APTT was lower than T1 (P < 0.05). The PLC, PT, and APTT of T4 in the control group were all lower than those of T1 (P < 0.05), and there was no significant difference between Fbg and T1 (P > 0.05). The PLC, Fbg, and PT of T4 in the observation group were higher than those in the control group, while APTT was lower than that in the control group (P < 0.05). The MoCA scores of patients in both groups on the 1st and 3rd day after operation were lower than those before operation, and the observation group was higher than that in the control group (P < 0.05). The BDNF and NGF of patients in both groups were lower than those before operation on the 1st day after operation, and the BDNF and NGF in the observation group were higher than those in the control group on the 1st and 3rd day after operation (P < 0.05). The mental disorder (2.94%) and DVT incidence (2.94%) in the observation group were lower than those in the control group (29.41%, 26.47%) (P < 0.05). CONCLUSION: Epidural anesthesia for patients with TKA can obtain better clinical effects, maintain stable hemodynamic and coagulation states, reduce stress response of patients at the same time, and reduce perioperative cognitive dysfunction and the incidence of DVT in patients.

Sini-San Regulates the NO-cGMP-PKG Pathway in the Spinal Dorsal Horn in a Modified Rat Model of Functional Dyspepsia.

The present study investigated the effect of Chinese medicine Sini-San (SNS) on visceral hypersensitivity in a rat model of functional dyspepsia (FD), and it explored related underlying mechanisms. The rat model of FD was developed by combining neonatal iodoacetamide (IA) treatment and adult tail-clamping. After SNS treatment, the behavior and electromyographic testing were performed to evaluate the visceromotor responses of rats to gastric distention. Immunofluorescence was used to detect the distribution of iNOS-positive cells in the spinal dorsal horn, while the real-time quantitative PCR and western blot were used for detection of the gene expression of c-fos, iNOS, and GABAb and protein levels of iNOS and GABAb in the spinal dorsal horn, respectively. The protein concentration of cGMP and PKG proteins in the spinal dorsal horn were quantified by enzyme-linked immunosorbent assay. In this study, SNS treatment significantly reduced the behavioral score and electromyographic response to graded intragastric distension pressure. The middle-dose of SNS treatment significantly reduced the distribution of iNOS-positive cells in the spinal dorsal horn of FD model rats. The gene expression of c-fos, iNOS, and GABAb and the protein contents of iNOS, GABAb, cGMP, and PKG in the spinal dorsal horn of FD model rats were restored to a normal level by middle-dose of SNS treatment. Our results suggest that Sini-San may alleviate the visceral hypersensitivity in FD model rats via regulation of the NO/cGMP/PKG pathway in the spinal dorsal horn.

Effect of TongXie-YaoFang on Cl(-) and HCO3 (-) Transport in Diarrhea-Predominant Irritable Bowel Syndrome Rats.

TongXie-YaoFang (TXYF) can effectively alleviate the symptoms of diarrhea-predominant irritable bowel syndrome (D-IBS) patients. However, the curative mechanism has not been fully clarified. The study was designed to investigate the effect of TXYF on the colonic ion transport induced by serotonin (5-HT) in D-IBS rats. A method of multiple stress (neonatal maternal separation (NMS) combined with restraint stress (RS)) was used to induce the D-IBS model. The model rats were randomly divided into two groups: NMS + RS group and TXYF-formula group, and the normal control (no handling) rats were classified as NH group. In the NMS + RS group, the change of short-circuit current (ΔI sc) induced by 5-HT was lower than that in the NH and TXYF-formula groups. After removing of the extracellular Cl(-) or HCO3 (-) or basolateral Na(+) or blocking the cystic fibrosis transmembrane conductance regulator (CFTR), Na(+)-K(+)-2Cl(-) cotransporter (NKCC), Na(+)-HCO3 (-) cotransporter, Cl(-)/HCO3 (-) exchanger, K(+) channel, or Na(+)/K(+)-ATPase, respectively, there was no difference in 5-HT-induced ΔI sc among the three groups. These data suggest that TXYF can regulate 5-HT-induced Cl(-) and HCO3 (-) secretion, possibly mediated by the combined action of CFTR, NKCC, Na(+)-HCO3 (-) cotransporter, Cl(-)/HCO3 (-) exchanger, K(+) channel, and Na(+)/K(+)-ATPase.

Effect of Aurantii Fructus Immaturus Flavonoid on the Contraction of Isolated Gastric Smooth Muscle Strips in Rats.

This study was designed to investigate the effect of Aurantii fructus immaturus flavonoid (AFIF) on the contraction of isolated gastric smooth muscle in rats and explore its underlying mechanisms. Isolated antral longitudinal smooth muscle strip (ALSMS) and pyloric circular smooth muscle strip (PCSMS) of rats were suspended in tissue chambers. The responses of ALSMS and PCSMS to administration of AFIF were observed. Cyclic guanosine monophosphate (cGMP) and protein kinase G (PKG) levels of PCSMS were measured by ELISA kits. In this study, AFIF showed no significant effect on ALSMS contraction, but it dose-dependently reduced the mean contraction amplitude of PCSMS. When the concentration of AFIF reached 3000 µg/mL, 6000 µg/mL, and 10000 µg/mL, its inhibitory effect on PCSMS contraction was significant. This effect of AFIF was weakened in Ca(2+)-rich environment. And Nω-nitro-L-arginine methyl (L-NAME), the inhibitor of nitric oxide synthase (NOS), significantly inhibited AFIF's action in comparison with control (P < 0.05). After incubation with AFIF for 30 min, levels of cGMP and PKG in PCSMS were significantly increased compared with control (P < 0.05). Our results suggest that AFIF has a dose-dependent diastolic effect on PCSMS in rats, which may be related to the regulatory pathway of NO/cGMP/PKG/Ca(2+).

[Effect of Zhizhu Pill on Gastric Smooth Muscle Contractile Response and Protein Expression of Growth Hormone Secretagogue Receptor in Functional Dyspepsia Rats].

OBJECTIVE: To study the therapeutic mechanism of Zhizhu Pill (ZP) for treating functional dyspepsia (FD) rats. METHODS: Totally 30 ten-day-old male rats were randomly divided into the normal control group (n =10) and the model group (n = 20). The FD rat model was induced using gastric administration of 0.1% iodoacetamide (IA) combined tail clamping. The model was evaluated when rats were 8-week old. Successfully modeled rats were randomly divided into the model group (n = 10) and the ZP group (n = 10). Rats in the normal group and the model group were administered with normal saline by gastrogavage, while those in the ZP group were administered with ZP Decoction (2 mL/100 g) by gastrogavage. All medication lasted for 7 successive days. The contractile activity in in vitro longitudinal gastric muscle was recorded using Power Lab biological signal collecting system. The expression of growth hormone secretagogue receptor (GHSR) in stomach of FD rats was detected using Western blot and immunohistochemistry (IHC). RESULTS: Compared with the normal group, average frequencies of gastric contraction and changing rates of amplitude obviously decreased in the model group (P < 0.05). Results of Western blot and IHC showed that the expression of GHSR decreased in the model group (P < 0.01). Compared with the model group, average frequencies of gastric contraction and changing rates of amplitude obviously increased in the ZP group (P < 0.05). Results of Western blot and IHC showed that the expression of GHSR increased in the ZP group (P < 0.01). CONCLUSION: ZP could promote the gastric motility in FD rats induced by gastric administration of IA combined tail clamping, and its mechanism might be related to up-regulating GHSR protein level.

Comparison of 18F-AIF-NOTA-PRGD2 and 18F-FDG uptake in lymph node metastasis of differentiated thyroid cancer.

UNLABELLED: A widespread application of integrin αvß3 imaging has been emerging in both pre-clinical and clinical studies. But few studies reported its value as compared with 18F-FDG PET, especially for differentiated thyroid cancer (DTC). In this study, we compared the tracer uptake of 18F-AIF-NOTA-PRGD2 and 18F-FDG in lymph node metastasis of DTC to evaluate 18F-AIF-NOTA-PRGD2 as compared with 18F-FDG. METHODS: 20 DTC patients with presumptive lymph node metastasis were examined with 18F-AIF-NOTA-PRGD2 and 18F-FDG PET/CT. 16 patients undergoing fine needle aspiration biopsy (FNAB) were evaluated by cytology results. For lesions without FNAB, the findings of clinical staging procedures served as the standard of reference (including neck ultrasound and serum thyroglobulin). RESULTS: A total of 39 presumptive lymph node metastases were visualized on PET/CT images. 35 lesions were confirmed as malignant by FNAB and other clinical findings. The mean 18F-AIF-NOTA-PRGD2 in radioactive iodine-refractory (RAIR) lesions and benign lesions were 2.5±0.9 and 2.8±0.9 respectively. The mean SUV for 18F-FDG in all malignant lesions was 4.5±1.6 while in benign lesions it was 3.3±1.2. For all malignant lesions, the mean SUV for 18F-FDG was significantly higher than that for 18F-AIF-NOTA-PRGD2 (P<0.05). No significant correlation was found between the SUVs of 18F-AIF-NOTA-PRGD2 and 18F-FDG for 35 lesions (r = 0.114, P = 0.515). Moreover, 15 lesions of which the diameter larger than 1.5 cm had higher 18F-AIF-NOTA-PRGD2 uptake as compared with the lesions smaller than 1.5 cm. CONCLUSION: Although most lymph node metastases of DTC showed abnormal uptake of 18F-AIF-NOTA-PRGD2, its diagnostic value was inferior to 18F-FDG. No correlation was found between the uptake of 18F-AIF-NOTA-PRGD2 and 18F-FDG, which may suggest the two tracers provide complementary information in DTC lesions.

[Study on the mechanism of action of total saponins of Panax notoginseng in ameliorating oxidative stress and insulin resistance in rats fed with high fat diet].

OBJECTIVE: To investigate whether total saponins of Panax notoginseng (tPNS) can ameliorate oxidative stress and insulin resistance (IR) in the high fat induced nonalcoholic fatty liver disease (NAFLD) rat model and to explore the relationship between oxidative stress and IR. METHODS: Totally 50 healthy rats were randomly divided into the normal control group (NC), the model group, the high dose tPNS group (at the daily dose of 160 mg/kg), the low dose tPNS group (at the daily dose of 80 mg/kg), and the bicyclol group (at the daily dose of 100 mg/kg), 10 in each group. Rats in the NC group were fed with standard forage. Those in the rest group were fed with high fat forage. Distilled water was given by gastrogavage to those in the NC group and the model group. Corresponding medication was performed for 4 weeks. Four weeks later Lee's index and body weight were measured. All rats were sacrificed to detect the wet weight of livers. Their sera was isolated and detected to calculate liver functions (serum ALT and AST levels). Levels of fasting blood glucose (FBG) and fasting insulin (FINS) were detected. Insulin sensitive index (ISI) and insulin resistance index (IRI) were calculated. Serum levels of TNF-alpha and malondialdehyde (MDA), contents of total superoxide dismutase (T-SOD), hydroxy radical level (-OH), and total antioxidant capacity (T-AOC) were measured. Pathological changes of livers was observed by HE staining of paraffin section. RESULTS: Compared with the NC group, rats' wet liver weight and Lee's index increased in the model group (P < 0.05), and results of light microscopy showed that obvious fatty degeneration occurred in livers. Compared with the model group, rats' wet liver weight and Lee's index, as well as ALT and AST could be obviously improved by tPNS and bicyclol (P < 0.05, P < 0.01). The fatty deposition of liver cells could also be alleviated. Compared with the NC group, serum levels of-OH, MDA, and TNF-alpha significantly increased, and activities of T-SOD and T-AOC decreased in the model group (P < 0.01), also accompanied with IR. Compared with the model group, concentrations of -OH, MDA, and TNF-alpha decreased after treated by tPNS (P < 0.05, P < 0.01), activities of T-SOD and T-AOC got recovered (P < 0.05, P < 0.01), and IR got obvious improvement (P < 0.01). CONCLUSION: The anti-oxidative stress effect and IR improving effect of tPNS might play partial roles in treating NAFLD.

[The protective mechanism study of fengshiqing recipe against bone destruction in CIA rats].

OBJECTIVE: To explore the protective mechanism of Fengshiqing Recipe (FR) against bone destruction in collagen-induced arthritis (CIA) rats. METHODS: Rats were divided into four groups in the experiment,i.e., the blank control group, the model group, the MTX group (MTX, 1 mg/1 000 g), and the FR group (24 g crude FR/kg). The CIA model was prepared except the blank control group. Medication was started in the MTX group and the FR group from the 14th day after modeling to the 56th day. The toe volume was measured on every Tuesday and Friday. Expression levels of serum IL-17, RANKL, MIP-1alpha were detected after 3-and 6-week intervention. The bone scintigraphy with nuclide (SPECT), bone mineral density (BMD), and the pathological section were observed to assess the intervention of drugs of heat clearing blood activating actions in the bone destruction of CIA rats. RESULTS: From the 10th day of modeling, the volume of both toes started to swell and reached the peak at about 21 days. It was obviously shrunk at about 30 days. Of them, the swelling degree was milder in the MTX group and the FR group than in the model group. Compared with the model group at the same phase, the levels of IL-17 and RANKL decreased in the MTX group after 3 weeks of intervention (P < 0.01, P < 0.05). The IL-17 level decreased in the FR group after three weeks of intervention (P < 0.05). The RANKL level decreased in the MTX group and the FR group after 6 weeks of intervention (P < 0.01, P < 0.05). Compared with the model group and the MTX group, the overall BMD and ankle BMD increased in the FR group after 6 weeks of intervention (P < 0.01, P < 0.05). The ankle ROI/mandible and the toe ROI/mandible were elevated in the FR group after 3 weeks of intervention (P < 0.05). Pathological results suggested that the joint lacunae was significantly widened, the hyperplasia of the synovial tissue was so severe, and the bone tissue was destroyed in the model group. Compared with the model group, the aforesaid conditions were significantly improved in the MTX group and the FR group. The cartilage structure was complete. CONCLUSION: QR could inhibit decreased BMD, prevent bone destruction, which might be achieved by down-regulating expression levels of IL-17, RANKL, and MIP-1alpha through the osteo immunological Th/RANKL system,inhibiting maturation and differentiation of osteoclasts, thereby, inhibiting bone destruction.

[Effect of electroacupuncture at "Ciliao"(BL 32) on c-fos expression in the sacral segment of spinal cord in rats with detrusor hyperreflexia].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Ciliao" (BL 32) on detrusor hyperreflexia and c-fos expression in the sacral segment of spinal cord in rats with spinal cord injury (SCI). METHODS: Thirty-seven adult female Sprague-Dawley rats were randomized into normal control (n=5), SCI model (n=16) and EA (n=16) groups. EA (20 Hz, 3 mA) was applied to bilateral BL 32 for 2 hours, once daily for 14 days. Intravesical pressure was detected by using a pressure transducer and a bioelectric amplifier. The expression of c-fos gene was detected by immunohistochemistry. RESULTS: In comparison with normal control group, the maximum intravesical pressure (MIVP) raised significantly in model group (P < 0.05), and the compliance of the bladder decreased remarkably (P < 0.05). While compared with model group, MIVP decreased significantly in SCI rats of EA group after EA intervention (P < 0.05), and the vesical compliance increased obviously (P < 0.05). In comparison with normal control group, the mean optical density (OD) value of c-fos immuno-reaction (IR) positive products increased significantly in the sacral cord after SCI in model group (P < 0.05), while compared with model group, the mean OD value of c-fos IR positive products in EA group declined evidently but still being higher than that of normal control group (P < 0.05), displaying a downregulation of c-fos expression after EA. CONCLUSION: Electroacupuncture at "Ciliao" (BL 32) can inhibit the overactivity of bladder in SCI rats and reduce the c-fos expression in the sacral cord, suggesting that the declined C-fibers' activity after EA may be one of its mechanism underlying improving detrusor hyperreflexia in spinal cord injury.

[Effect of fengshiqing on interleukin-4, gamma-interferon and chemotactic factor in rats with collagen type II].

OBJECTIVE: To study the regulatory effect of fengshiqing (FSQ) on interleukin 4 (IL-4), gamma-interferon (gamma-IFN), macrophage inflammatory protein 1alpha (MIP-1alpha) and collagen type II antibody (C II Ab) in serum and supernatant of synovial cell culture of rat with rheumatoid arthritis (RA), to explore the mechanism of action of clearing-heat and activating blood method for treatment of RA. METHODS: RA rat model was induced by C II Ab combined with Freund's complete adjuvant, and the levels of IL-4, gamma-IFN, MIP-1alpha and C II Ab in serum and supernatant of synovial cell were detected by ELISA. RESULTS: As compared with the normal group, serum level of C II Ab in the model group was significantly higher (P < 0.01), serum and supernatant contents of IL-4 on the 14th and 28th day of modeling were lower and those of gamma-IFN and MIP-1alpha were higher, the difference showed statistical significance (P < 0.05 or P < 0.01). After being treated with FSQ and IL-4 contents in serum and supernatant as well as MIP-1alpha in supernatant restored on the 14th day (P < 0.05 or P < 0.01), while all the indexes restored on the 28th day. CONCLUSION: FSQ could evidently up-regulate the level of IL-4 and down-regulate that of MIP-1alpha in serum and local synovial membrane in RA rats, and shows a suppressive trend of gamma-IFN, so as to maintain the Th1/Th2 equilibrium, suppress the cellular and humoral immune response in the local synovial membrane, and alleviate the chronic changes of arthritis, synovitis and vasculitis.

[Effect of Qiangxin Fumai granule on myocyte apoptosis of sinus node and Bax, Bcl-2, Fas-L gene protein in rabbits of sinoatrial ischemia/reperfusion].

OBJECTIVE: To explore the molecular mechanism of Qiangxin Fumai granule (QFG, an effective Chinese composite drug) in preventing and treating sick sinus syndrome (SSS). METHOD: Rabbit model of sinoatrial ischemia/reperfusion was established by occluding and loosening the root of right coronary artery. Effect of QFG on cell apoptosis was observed by TUNEL method, and its effect on apoptotic related gene Bax, Bcl-2 and Fas-L gene protein expression was observed by immunohistochemical method. Average light density values of the expression of Bax, Bcl-2 and Fas-L of SAN cells was determined by Imagepro Plus image analysis system. RESULT: Sinoatrial injury induced by ischemia/reperfusion could cause evident sinoatrial cell apoptosis, enhance Fas-L gene protein expression and obviously enhance Bax gene protein expression, reduce Bcl-2/Bax ratio. QFG could significantly down-regulate Fas-L and Bax gene protein expression, up-regulate Bcl-2/Bax ratio, significantly inhibit and block the sinoatrial cell apoptosis. CONCLUSION: To inhibit and block the event of cell apoptosis through regulating Bax, Bcl-2 and Fas-L gene protein expression in sinoatrial node after ischemia/reperfusion might be one of the mechanisms of QFG in preventing and treating sinoatrial ischemia/reperfusion injury of SSS.

[Variation of TFAR-19 protein expression in the thymus of emotional stress mice and the regulatory effect of Modified Xiaoyao Pill].

OBJECTIVE: To study the variation of TFAR-19 protein expression and Annexin-V apoptosis protein proportion in the mice thymus cell apoptosis procedure induced by water platform environment or electric emotional stress and the regulatory effect of Modified Xiaoyao Pill (MXP). METHODS: The mouse emotional stress model was established by water platform equipment or electrical stimulation. The serum glucocorticoid was detected by radioimmunoassay, the TFAR-19 protein was detected by flow cytometry analysis, and Annexin-V apoptosis protein proportion was calculated by immunofluorescence technique. RESULTS: In the groups of mouse stressed by water platform environment, the level of serum glucocorticoid, the TFAR-19 protein expression and the Annexin-V apoptosis protein proportion increased in the thymus cell along with the stress time prolonging (P<0.05 or P <0.01). The serum glucocorticoid level in mice treated with MXP was lower than that in the untreated group (P <0.05). In the groups of emotional stressed mouse established by electrical stimulation, the above-mentioned variations also revealed. All these variations could be alleviated with MXP (P<0.05). CONCLUSION: The water platform environment stress is a chronic continuous stress and electrical stimulation is an acute smooth stress, both of them could damage thymus function through neuro-endocrineo-immune network, but different in duration for causing severe injury. Chinese medicine MXP can alleviate the damage of thymus induced by either of them to certain degree.

[Rules of protein expression of proto-oncogene (c-Fos/c-Jun) in different brain areas and nucleus of psychological stressed mice and the regulatory effect of modified Xiaoyao Pill].

OBJECTIVE: To study the rules of protein expression of proto-oncogene (c-Fos/c-Jun) in different brain areas and nucleus of psychological stressed mice and the regulatory effect of modified Xiaoyao Pill (SXP). METHODS: The mouse psychological stress model was established by electrical stimulation; SXP was administrated at the dose of 2 mg/g; the protein expression of c-Fos and c-Jun in different brain areas and nucleus, including hippocampus (CA1-4), central amygdaloid nucleus (CAN), paraventricular nucleus (PVN) and supraoptic nucleus (SON), were detected by immunohistochemical method. RESULTS: The protein expressions of c-Fos and c-Jun in all the tested brain areas of model mice 3 h after being stressed for 1, 3 or 5 times, were significantly higher than those of the normal mice (P < 0.01); After being stressed for one time, the expression at 1 h after stimulation was lower than that at 3 h after stimulation (P < 0.05), the expression in mice treated with SXP was lower than that in the untreated group, 3 h after three or five times of stress (P < 0.05 or P < 0.01). CONCLUSION: The protein expression of c-Fos and c-Jun began to rise 1 h after psychological stress and reached the peak at the 3rd h. That of c-Fos dropped to the normal level approximately after 6 h, but the dropping did not happen in expression of c-Jun, it remained on the high level unweakened after repeated stimulation; SXP can remarkably down-regulate the proto-oncogene (c-Fos and c-Jun) expressions after psychological stress in mice.

[Effects of blockage of hypothalamic-pituitary-adrenal cortex axis by metyrapone and Jiawei Xiaoyao Pills on immune system in mice exposed to chronic emotional stress].

OBJECTIVE: To explore the effects of Jiawei Xiaoyao Pills (JWXYP) on immune system of mice exposed to chronic emotional stress, and to compare its effects with blockage of hypothalamic-pituitary-adrenal cortex axis (HPAA) by metyrapone. METHODS: Eighty male mice were randomly divided into eight groups: normal saline-treated group, normal saline-treated stress group, JWXYP-treated group, JWXYP-treated stress group, metyrapone-treated group, metyrapone-treated stress group, metyrapone and JWXYP-treated group and metyrapone and JWXYP-treated stress group. A box of electrical shock was used to induce chronic emotional stress in mice. The metyrapone was applied to blocking the HPAA. The JWXYP, a classical formula of traditional Chinese medicine, which can alleviate the damages caused by chronic emotional stress, was also used to compare its effects with that of metyrapone. The body weight, thymus index, rate of apoptosis in thymus, serum concentration of glucocorticoid, activity of natural killer cells, lymphocyte transmission rate of mice were all measured and examined after interventions. The pathological changes of thymus tissue were observed. RESULTS: The thymus index, activity of natural killer cells and lymphocyte transmission rate were lower while the rate of apoptosis in thymus as well as the severity degree of pathological damages in thymus tissue were increased in the different drug-treated stress groups as compared with those in the corresponding drug-treated groups without stress. The activity of natural killer cells and the lymphocyte transmission rate induced by lipopolysaccharide were increased while the serum concentration of glucocorticoid and the severity degree of pathological damages in thymus tissue were decreased in both the metyrapone-treated stress group and JWXYP-treated stress group as compared with those in the normal saline-treated stress group. The combined intervention of metyrapone and JWXYP did not show better effects on immune system in mice exposed to chronic emotional stress than single metyrapone or JWXYP intervention. CONCLUSION: Blockage of HPAA by metyrapone intervention shows a significant protective effect on immune system in mice exposed to chronic emotional stress, and the JWXYP also exerts a similar protective effect against damages induced by chronic emotional stress. The HPAA may be one of the action targets of protective effects of JWXYP.