LncRNA TSLNC8 synergizes with EGFR inhibitor osimertinib to inhibit lung cancer tumorigenesis by blocking the EGFR-STAT3 pathway.

The roles of lncRNA TSLNC8 and its synergetic effects with osimertinib remain unknown in lung cancer. qRT-PCR or western blotting was performed to determine the expression levels of TSLNC8, EGFR and STAT3. Colony formation and MTT assays were used to evaluate cell proliferation. Transwell and wound healing assays were performed to assess migration and invasion abilities. Flow cytometry with Annexin V/PI staining was used to detect changes in cell apoptosis. Nude mice subcutaneous tumor model was constructed and used for validating the effects of TSLNC8 and osimertinib in vivo. Expression of TSLNC8 was down-regulated in clinical lung cancer tissues and cell lines. TSLNC8 overexpression or osimertinib administration led to promotion of apoptosis and inhibition of cell proliferation, migration and invasion, as well as deactivation of the EGFR-STAT3 pathway, whereas TSLNC8 knockdown had opposite effects. Moreover, the above effects of osimertinib were remarkably enhanced by TSLNC8 overexpression and inhibited by TSLNC8 knockdown, respectively. Meanwhile, the effects of TSLNC8 overexpression were reversed by STAT3 activation or EGFR overexpression. In the animal model, combination of TSLNC8 overexpression and osimertinib administration resulted in efficient suppression of tumor growth. In this study, we revealed a TSLNC8-EGFR-STAT3 signaling axis in lung cancer, and TSLNC8 overexpression significantly enhanced the anti-tumor effects of osimertinib via inhibiting EGFR-STAT3 signaling.

Effect of Comprehensive Therapy based on Chinese Medicine Patterns on Self-Efficacy and Effectiveness Satisfaction in Chronic Obstructive Pulmonary Disease Patients.

OBJECTIVE: To evaluate the effect of comprehensive therapy based on Chinese medicine (CM) patterns on self-efficacy and satisfaction with its effectiveness in patients with chronic obstructive pulmonary disease (COPD). METHODS: A total of 216 patients were randomly divided into the trial group (n =108) and the control group (n=108) based on the stratified and block randomization design. Patients in the trial group were treated with conventional Western medicine combined with Bufei Jianpi Granules (), Bufei Yishen Granules (), and Yiqi Zishen Granules () according to the CM patterns respectively, and patients in the control group were treated with conventional Western medicine. The COPD Self-Efficacy Scale (CSES) and the Effectiveness Satisfaction Questionnaire for COPD (ESQ-COPD) were employed in a 6-month treatment and in further 6 month follow-up visit. RESULTS: Among the 216 patients, 191 patients (97 in the trial group and 94 in the control group) fully completed the study. After 12-month treatment and follow-up, the mean scores of the trial group all continued to increase over time, which were significantly higher than those of the control group (P <0.05), and the improvement in the following trial group domain: negative affect domain (12.13%), intense emotional arousal domain (12.21%), physical exertion domain (11.72%), weather/environmental domain (13.77%), behavioral risk domain (7.67%) and total score (10.65%). The trial group also exhibited significantly higher mean scores in the ESQ-COPD (P <0.05) and the improvement in the following domain: capacity for life and work domain (30.59%), clinical symptoms domain (53.52%), effect of therapy domain (35.95%), convenience of therapy domain (35.54%), and whole effect domain (52.47%). CONCLUSIONS: Bufei Jianpi Granules, Bufei Yishen Granules and Yiqi Zishen Granules can improve the self-efficacy and satisfaction of COPD patients.

An evaluation of activity tolerance, patient-reported outcomes and satisfaction with the effectiveness of pulmonary daoyin on patients with chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Pulmonary Daoyin (PD) (evolved from ancient Chinese daoyin skills), is a rehabilitation technology that combines specially designed movements of the arms and body and controlled breathing exercises, to improve the physiological and psychological status of patients with chronic respiratory disease. Pulmonary rehabilitation is effective for patients with chronic obstructive pulmonary disease (COPD), and the efficacy of PD is unknown. The aim of this study is to investigate the effect of a PD program in enhancing activity tolerance, patient-reported outcomes and satisfaction with the effectiveness on patients with COPD. MATERIALS AND METHODS: The multi-center, randomized controlled trial was conducted from November 2011 to June 2012 in local communities in cities of the 11 research centers in China. It included COPD patients (moderate to very severe) who were recruited from an outpatient clinic. A randomized controlled study included 464 COPD patients who were randomly allocated either to the PD group, participating in a 3-month, ten times-weekly supervised PD-based pulmonary rehabilitation program, or to a control group continuing with regular medical treatment alone. Data were gathered using the 6-minute walking distance (6MWD) test, COPD patient-reported outcomes (COPD-PRO) and Effectiveness Satisfaction Questionnaire for COPD (ESQ-COPD), which was filled out at baseline and 3 months post-intervention. SAS 9.2 was used for statistical analysis. RESULTS: Of the 464 patients in the study, 461 were included in the full analysis set (FAS); 429 were in the per-protocol analysis set (PPS). After 3-month intervention, there was a significant difference between the two groups in 6MWD (FAS; P=0.049; PPS; P=0.041), total score and all domains of COPD-PRO (FAS; P=0.014; PPS; P=0.003) and ESQ-COPD (FAS; P=0.038; PPS; P<0.001). CONCLUSIONS: The PD program was able to improve the activity tolerance level and satisfaction of COPD patients because of its effectiveness.

Bufei Yishen granules combined with acupoint sticking therapy suppress oxidative stress in chronic obstructive pulmonary disease rats: Via regulating peroxisome proliferator-activated receptor-gamma signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) is clinically used under the guidance of its unique theory system. Bufei Yishen (BY) granules, an oral Chinese herbal formula, is confirmed effective for treating the syndrome of lung-kidney qi deficiency in chronic obstructive pulmonary disease (COPD) patients. Shu-Fei Tie ointment is another prescription for acupoint sticking (AS) therapy based on the theory of treating an internal disease by external treatment on proper acupoints. The beneficial effects of BY granules combined with Shu-Fei Tie have been proved in previous clinical trials. However, the underlying mechanism remains unclear. The present study was initiated to explore the antioxidative mechanism of the integrated therapy of BY granules and acupoint sticking via regulating by peroxisome proliferator activated receptor-gamma (PPARγ) signaling in a cigarette-smoke/bacterial exposure induced COPD rat model. MATERIALS AND METHODS: Rats were randomized into Control, Model, BY, AS, BY+AS and aminophylline (APL) groups. COPD rats were induced by cigarette-smoke and bacterial exposures, and were administrated with normal saline, BY granules, AS, BY+AS or aminophylline from week 9 and sacrificed at week 20. Activity of superoxide dismutase (SOD) and levels of methane dicarboxylic aldehyde (MDA) in peripheral blood and bronchoalveolar lavage fluid (BALF) were determined by hydroxylamine and thiobarbituric acid methods. The gene and protein expressions of PPARγ in the lung tissues were analyzed by quantitative polymerase chain reaction and western blot. RESULTS: Serum and BALF SOD decreased significantly in Model group (P<0.01), while MDA increased (P<0.01). Compared to COPD rats, serum SOD was higher in all treatment groups (P<0.01), and BALF SOD was higher in BY and BY+AS groups (P<0.01); serum and BALF MDA was lower in all treatment groups (P<0.01). Serum and BALF SOD was higher in BY+AS group than in AS group, while MDA was lower (P<0.05). BALF SOD increased in BY+AS group compared with APL group, while MDA decreased (P<0.05). PPARγ mRNA and protein and the phosphorylation of PPARγ (p-PPARγ) decreased in COPD rats (P<0.01), and increased in all treatment groups (P<0.01). PPARγ mRNA was higher in BY+AS group than in AS group (P<0.05), PPARγ and p-PPARγ were higher in BY+AS group than in AS and APL groups (P<0.05, P<0.01); PPARγ protein was higher in BY group than in APL group (P<0.05). CONCLUSION: Bufei Yishen granules, Shu-Fei Tie and their combination have beneficial effects in stable COPD, and can attenuate the oxidative stress, and the activation of PPARγ signaling might be involved in the underlying mechanisms, but there are no obvious synergistic effect of Bufei Yishen granules and Shu-Fei Tie.

Development and validation of a patient reported outcome instrument for chronic obstructive pulmonary diseases.

OBJECTIVE: To develop and validate a specific patient reported outcome (PRO) for chronic obstructive pulmonary disease (COPD) patients (COPD-PRO) at a set of standardized procedures. METHODS: Literature analysis, interview and group discussion were performed to draft an initial model of COPD-PRO. Thereafter, 65 clinicians and experts throughout China reviewed the draft scale. Then cognitive debriefing interviews with 40 patients were conducted to assess respondent comprehension of the scale. After that, the revised scale was validated through pre-testing and field-testing. Finally, the psychometric properties of the COPD-PRO were evaluated by indicators such as validity, reliability and responsiveness based on the data from 230 patients. RESULTS: The COPD-PRO contained 17 items in 3 domains: amelioration of clinical symptoms, satisfaction of health condition and satisfaction of treatment effect. The Cronbach's α, Split-half coefficient and test-retest coefficient were 0.806, 0.744, 0.703, respectively; the correlation coefficients between domains and overall scale were 0.835-0.963; 5 factors were extracted according to the conceptual model. The differences of the scale scores before and after treatment were statistically significant (P=0.000). CONCLUSIONS: The COPDPRO has good validity, reliability and responsiveness. The COPD-PRO could provide patients' response to the treatments and then evaluate the effect of treatment in a standardized way.

The effective evaluation on symptoms and quality of life of chronic obstructive pulmonary disease patients treated by comprehensive therapy based on traditional Chinese medicine patterns.

OBJECTIVE: To evaluate the efficacy of comprehensive interventions based on the three TCM patterns on symptoms and quality of life of COPD patients. DESIGN: An open-label, randomized, controlled trial. SETTING: Four hospitals in China. INTERVENTION: 352 patients were randomly divided into two groups. Patients in the trial group were given conventional Western medicine and Bu-Fei Jian-Pi granules, Bu-Fei Yi-Shen granules and Yi-Qi Zi-Shen granules respectively; patients in the control group were given conventional Western medicine. Data collection was performed at baseline, in the 3rd and 6th month during the treatment period, and the 12th month during the follow-up period. OUTCOMES: Symptoms, including cough, sputum, pant, chest tightness, short of breath, lassitude, cyanosis and symptom total score; quality of life, measured by the WHOQOL-BREF questionnaire and adult COPD quality of life questionnaire (COPD-QOL). RESULTS: Of the 352 patients, 306 fully completed the study. After treatment and follow-up, there were significant differences between two groups in the following: cough, sputum, pant, chest tightness, shortness of breath, lassitude score and symptom total score (P<.05); physical, psychological, social and environment domain (P<.05) of the WHOQOL-BREF; daily living ability, social activity, depression symptoms and anxiety symptoms domain (P<.05) of the COPD-QOL. There were no differences between two groups in cyanosis and adverse events. CONCLUSION: Based on the TCM patterns, Bu-Fei Jian-Pi granules, Bu-Fei Yi-Shen granules and Yi-Qi Zi-Shen granules have beneficial effects on symptoms and quality of life of COPD patients.

Functional and psychosocial effects of pulmonary Daoyin on patients with COPD in China: study protocol of a multicenter randomized controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major public health problem worldwide. Pulmonary rehabilitation (PR) is an established intervention for the management of patients with COPD. Exercise training is an important part of PR, and its effectiveness in patients with COPD is well established. However, alternative methods of PR training such as Daoyin have not been appropriately studied. Hence, alternative forms of exercise training that require less exercise equipment and no specific training place should be evaluated. This paper describes the study protocol of a clinical trial that aims to determine if pulmonary Daoyin training will improve the exercise capacity and psychosocial function of patients with COPD in China. METHODS AND DESIGN: A multicenter, randomized, controlled trial will be conducted. A total of 464 patients meeting the inclusion criteria will be enrolled into this study with 232 patients in each of the trial group and the control group. Based on patient education, patients in the trial group will receive pulmonary Daoyin and continue with their usual therapy for three months. In the control group, patients will continue with their usual therapy. The primary outcome measures are exercise capacity assessed by the six-minute walking distance test and lung function. Secondary outcomes include dyspnea and quality of life. Measurements will be taken at baseline (month 0) and after the study period (month 3). DISCUSSION: It is hypothesized that pulmonary Daoyin will have beneficial effects in improving exercise capacity and psychosocial function of patients with stable COPD, and will provide an alternative form of exercise training that is accessible for the large number of people with COPD. TRIAL REGISTRATION: This trial has been registered in ClinicalTrials.gov. The identifier is NCT01482000.

Effects of comprehensive therapy based on traditional Chinese medicine patterns in stable chronic obstructive pulmonary disease: a four-center, open-label, randomized, controlled study.

BACKGROUND: Traditional Chinese medicine (TCM) has been used to treat chronic obstructive pulmonary disease (COPD) for many years. This study aimed to evaluate the efficacy and safety of the comprehensive therapy based on the three common TCM patterns in stable COPD patients. METHODS: A four-center, open-label randomized controlled method was conducted. A total of 352 patients were divided into the trial group (n = 176, treated with conventional Western medicine and Bu-Fei Jian-Pi granules, Bu-Fei Yi-Shen granules, and Yi-Qi Zi-Shen granules based on the TCM patterns respectively) and the control group (n = 176, treated with conventional Western medicine). The frequency and duration of acute exacerbation, lung function, clinical symptoms, 6-minute walking distance (6MWD), dyspnea scale and quality of life were observed during a 6-month treatment period and at a further 12-month follow-up. RESULTS: A total of 306 patients completed the study fully. The full analysis set (FAS) population was 350 and the per-protocol analysis set (PPS) population was 306. After the 6-month treatment and 12-month follow-up, there were significant differences between the trial and control group in the following: frequency of acute exacerbation (FAS: P = 0.000; PPS: P = 0.000); duration of acute exacerbation (FAS: P = 0.000; PPS: P = 0.001); FEV1 (FAS: P = 0.007; PPS: P = 0.008); symptoms (FAS: P = 0.001; PPS: P = 0.001); 6MWD (FAS: P = 0.045; PPS: P = 0.042); dyspnea scale (FAS: P = 0.002; PPS: P = 0.004); and physical domain (FAS: P = 0.000; PPS: P = 0.000), psychological domain (FAS: P = 0.008; PPS: P = 0.011), social domain (FAS: P = 0.001; PPS: P = 0.000) and environment domain (FAS: P = 0.015; PPS: P = 0.009) of the WHOQOL-BREF questionnaire. There were no differences between the trial and control group in FVC, FEV1% and adverse events. CONCLUSIONS: Based on the TCM patterns, Bu-Fei Jian-Pi granules, Bu-Fei Yi-Shen granules and Yi-Qi Zi-Shen granules have beneficial effects on measured outcomes in stable COPD patients over the 6-month treatment and 12-month follow-up, with no relevant between-group differences in adverse events. TRIAL REGISTRATION: This trial was registered at Chinese Clinical Trial Register Center, ChiCTR-TRC-11001406.

Prognostic factors for community-acquired pneumonia in middle-aged and elderly patients treated with integrated medicine.

OBJECTIVE: To identify prognostic factors in middle-aged and elderly patients with community-acquired pneumonia (CAP) who underwent integrated interventions involving traditional Chinese medicine (TCM) and modern medicine. METHODS: Patients aged > or =45 years and diagnosed with CAP were divided into a middle-aged cohort (45-59 years) and an elderly cohort (> or =60 years), and clinical data comprising 75 predictor variables in seven classes were collected. After replacing missing data, calibrating multicenter differences and classifYing quantitative data, univariate and multivariate analysis were performed. RESULTS: On multivariate analysis, eight independent risk factors--respiration rate, C reactive protein (CRP), cost of hospitalization, anemia, gasping, confusion, moist rales and pneumonia severity index (PSI)--were correlated with the outcome "not cured" in the elderly cohort. Nine factors--neutrophil percentage (Neu%), blood urea nitrogen (BUN), time to clinical stability, appetite, anemia, confusion, being retired or unemployed, Gram-negative bacterial infection and educational level were correlated with not cured in the middle-aged cohort. CONCLUSION: Independent predictive risk factors correlated with adverse outcomes in elderly patients were higher respiration rate, CRP > or = four times the mean or median for the patient's center, cost of hospitalization >11,323 RMB and PSI >11, plus anemia, gasping, confusion and moist rales; those in middle-aged patients were higher Neu%, BUN > or = mean or median, loss of appetite, anemia, confusion, being retired or unemployed and lower educational level. Gram-negative bacterial infection and time to clinical stability >9 days were protective factors.

Diagnostic value of computed tomography in chronic obstructive pulmonary disease: a systematic review and meta-analysis.

INTRODUCTION: Computed tomography (CT) has been approved for diagnosing chronic obstructive pulmonary disease (COPD). The diagnostic accuracy, however, has never been examined in a systematic review. Therefore, we conducted a meta-analysis to evaluate the accuracy of CT in diagnosing COPD. METHODS: Articles reporting diagnostic accuracy of CT for COPD were searched from seven electronic databases and hand searching. Two reviewers independently extracted data and assessed methodological quality. Sensitivity (SEN), specificity (SPE), positive and negative likelihood ratios (LR+ and LR-, respectively), and diagnostic odds ratios (DOR) were pooled using a bivariate model. The diagnostic performance of overall test also was assessed using the visual power of the ROC plot to present the bivariate model. Potential between-study heterogeneity was explored using subgroup analyses. RESULTS: Data were extracted from 8 studies that met the inclusion criteria. All summary measures were grossly heterogeneous and therefore would not be appropriately summarized. These studies were further stratified by type of imaging technique and test index. The summary estimates of CT for COPD were as follows: SEN, 0.83(95% CI, 0.73-0.89); SPE, 0.87(95% CI, 0.70-0.95); LR+, 6.2(95% CI, 2.5-15.5); LR-, 0.20(95% CI, 0.12-0.34); and DOR, 31(95% CI, 8-116). The five summary estimates of CT on the lung density were 0.80 (95% CI, 0.74-0.84), 0.77(95% CI, 0.58-0.89), 3.5(95% CI, 1.8-6.9), 0.26(95% CI, 0.20-0.34) and 13(95% CI, 6-32), respectively. CONCLUSIONS: The current meta-analyses suggest that quantitative measures of CT may be useful to diagnose COPD. Developed CT technology may improve the accuracy of diagnosis. Further studies assessed diagnostic performance of CT are needed.

Bu-Fei Yi-Shen granule combined with acupoint sticking therapy in patients with stable chronic obstructive pulmonary disease: a randomized, double-blind, double-dummy, active-controlled, 4-center study.

ETHNOPHARMACOLOGICAL RELEVANCE: Bu-Fei Yi-Shen granule combined with acupoint sticking therapy has been used in the patients with stable chronic obstructive pulmonary disease (COPD) as major traditional interventions for the treatment of the disease. AIM OF THE STUDY: The objective of this study was to evaluate the efficacy and safety of traditional Chinese herbal medicine, the Bu-Fei Yi-Shen granule combined with acupoint sticking therapy in patients with stable COPD. METHODS: A 4-center, double-blinded, double-dummy and randomized controlled method was conducted. 244 patients who were divided into the trial group (n=122, treated with Bu-Fei Yi-Shen granule combined with Shu-Fei Tie acupoint sticking therapy and oral placebo sustained-release theophylline) and the control group (n=122, treated with oral sustained-release theophylline and placebo Bu-Fei Yi-Shen granule combined with placebo Shu-Fei Tie acupoint sticking therapy). The frequency and duration of acute exacerbation, lung function, clinical symptoms, six-minute walking distance, dyspnea grade and quality of life were observed during the 4-month treatment period, and for a further 6 months follow-up. RESULTS: Two hundred and twenty one patients fully completed the study, intent-to-treat (ITT) population was 234 and per-protocol (PP) population was 221. After treatment for 4 months and follow-up for 6 months, there were differences between the experimental and control group in frequency of acute exacerbation (ITT: P=0.007, P=0.013; PP: P=0.045, P=0.046); duration of acute exacerbation (ITT: P=0.030, P=0.005; PP: P=0.048, P=0.006); scores of symptoms (ITT: P=0.000, P=0.000; PP: P=0.000, P=0.000); six-minute walking distance (ITT: P=0.002, P=0.001; PP: P=0.002, P=0.001); dyspnea grade (ITT: P=0.014, P=0.009; PP: P=0.018, P=0.012); physiological aspects (ITT: P=0.003, P=0.000; PP: P=0.001, P=0.000); psychological aspects (ITT: P=0.007, P=0.001; PP: P=0.001, P=0.000) and environment aspects (ITT: P=0.003, P=0.000; PP: P=0.001, P=0.000) of the WHOQOL-BREF questionnaire. There were no differences between the experimental and control group in FVC, FEV1 and FEV1% and adverse events. CONCLUSIONS: Bu-Fei Yi-Shen granule combined with acupoint sticking therapy showed beneficial effects for patients with stable COPD in the measured parameters over the 4-month treatment period and 6 months follow-up, with no relevant between-group differences in adverse events.

[CCERW: a new rule to predict treatment failure in patients with community-acquired pneumonia in middle aged and elderly people].

OBJECTIVE: To develop and validate a clinical rule to predict treatment failure in middle-aged and elderly patients suffering from community-acquired pneumonia (CAP) in China, and to compare it with other prognostic rules. METHODS: Data of 58 variables affiliated to 6 aspects, including demographics, underlaying diseases, previous status, complications, symptoms, signs and laboratory examination results from the CAP patients aged≥45 years admitted to the respiratory departments in three university affiliated hospitals between December 17, 2006 and December 22, 2008 were enrolled prospectively and then validated in two groups to create a derivation cohort with 75% of the patients for rule development and an internal validation cohort with the other 25% for internal test. An external validation cohort was formed at the same time with patients admitted to the other university affiliated hospital for external test. The single outcome was treatment failure at the time of 14 days after admitted or at discharge from hospital. Univariate analysis, multivariate analysis and receiver operating characteristics (ROC) curve were used for the rule establishment, assessment and comparison among the pneumonia severity index (PSI), CURB65 [confusion, blood urea nitrogen>6.8 mmol/L, respiratory rate (RR)≥30 breaths per minute, systolic blood pressure (SBP)<90 mm Hg (1 mm Hg=0.133 kPa) or diastolic blood pressure (DBP)≤60 mm Hg, age≥65 years] and CRB65 (confusion, RR≥30 breaths per minute, SBP<90 mm Hg or DBP ≤60 mm Hg, age≥65 years). RESULTS: The data of a total of 539 patients in three hospitals were enrolled for analysis. Of those, 400 and 139 patients were randomly allocated into the derivation cohort or internal validation cohort respectively. Meanwhile, 159 patients were enrolled in the external validation cohort. Analyzing the data from 400 patients in the derivation cohort, 33 variables of 6 aspects had significant difference between cure and treatment failure outcome in the univariate analysis. Then, in the multivariate analyses, five independent predictive factors showed significant difference, including confusion (C), creatinine<60 µmol/L, electrolyte disturbances (E), respiratory failure (R), white blood cell (WBC)>7.5×10(9)/L. A clinical prediction rule CCERW based on these variables showed that the treatment failure outcome increased directly with increasing scores: 5.5%-9.1%, 12.8%-20.0% and 31.0%-40.5% for scores of 0-1, 2 and 3-6, respectively. ROC curve analysis yielded an area under the curve (AUC) for CCERW of 0.709 [95% confidence intervals (95%CI) 0.638-0.780], 0.725 (95%CI 0.613-0.838) and 0.686 (95%CI 0.590-0.782) in the derivation, internal and external validation cohorts respectively; and in the same manner, of 0.710 (95%CI 0.659-0.761) for total 698 patients, which was better than PSI, CURB65 and CRB65, at 0.667 (95%CI 0.614-0.719), 0.648 (95%CI 0.592-0.705), and 0.584 (95%CI 0.530-0.638), respectively. CONCLUSION: CCERW can help physicians to distinguish high and low risk leading to treatment failure in middle-aged and elder patients with CAP, and has better predictable capability than PSI, CURB65 and CRB65. We prudent recommend the simple rule can be used in the middle-aged and elder patients with CAP of Han race people in China.

[Relationship between the changes in ischemia/reperfusion cerebro-microvessel basement membrane injury and gelatinase system in senile rat].

OBJECTIVE: To study the relationship of cerebro-microvessel basement membrane injury and gelatinase system after cerebral ischemia/reperfusion (I/R) in aged rats. METHODS: Cerebral I/R injury model was reproduced by intraluminal silk ligature thrombosis of the middle cerebral artery occlusion (MCAO). Rats were divided randomly into sham control and I/R groups in young rats [ischemia 3 hours (I 3 h) and reperfusion 6 hours (I/R 6 h), 12 hours (I/R 12 h), 24 hours (I/R 24 h), 3 days (I/R 3 d), 6 days (I/R 6 d)], and sham control group and I/R group in aged rats (I 3 h and I/R 6 h, I/R 12 h, I/R 24 h , I/R 3 d, I/R 6 d). The change in cerebro-cortex microvessel basement membrane structure, basement membrane type IV collagen (Col IV) and laminin (LN) contents, matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) expression in every group were determined with immunohistochemical method and zymogram analysis. RESULTS: With the increase in age, Col IV and LN contents of the microvessel basement membrane were increased, and MMP-2 and MMP-9 expressions were stronger. With prolongation of I/R, the degradation of microvessel basement membrane components (Col IV and LN) was positively correlated with the duration of cerebral I/R. MMP-2 expression was increased gradually, and MMP-9 and TIMP-1 expression increased at the beginning and decreased subsequently. Col IV(I 3 h, I/R 6 h , I/R 12 h), LN (I 3 h, I/R 6-24 h), MMP-2 (I 3 h, I/R 6 h-6 d) and MMP-9 (I 3 h, I/R 6-24 h) expression level in aged rats with I/R injury were higher, and TIMP-1 (I/R 24 h) expression was lower than those in young rats (P<0.05 or P<0.01). In addition, changes in MMP-2 and MMP-9 contents as determined by zymogram analysis method coincided with their immunoexpression. CONCLUSION: With the increase of age, alteration in membrane components of cerebro-microvessel basement membrane in rats is related with MMPs and TIMP. Cerebro-microvessel basement membrane injury is more serious in aged rats than that of young rats. Changes in cerebro-microvessel basement membrane injury in aged rats is related with gelatinase system change.

[Modulation effect of naomaitong on gelatinase system after cerebral ischemia/reperfusion in rats LI].

OBJECTIVE: To study the modulation effect of Naomaitong on gelatinase system after cerebral ische-Focal cerebral I/R rat model was duplicated by method of the intralumimia/reperfusion (I/R) in rats. METHOD: nal filament technique. Rats were randomly divided into the sham-operative group, the model group, the Naomaitong group and the Nimodipine group, the latter three groups were also divided into the 3 hrs after ischemia group, and 6 hrs, 12 hrs, 24 hrs, 3 d, 6 d after IR groups. Immunohistochemical method and zymogram analysis method, etc. were adopted to observe the change of microvessel structure, gelatinase and its inhibitor expression. RESULTS: MMP-2 (IR 24 h-6 d)and MMP-9 (I/R 12 h-3 d) expression levels could be lowered and TIMP-1 expression level (IR 24 h-6 d) improved by Naomaitong. Besides, comparison of MMP-2 and MMP-9 content in zymogram analysis in each group showed that changes of its quantity were in accordance with the laws of immune expression. CONCLUSION: The protective effect of Naomaitong on cerebromicrovessel basement membrane injury in rats is related to its modulation on gelatinase system.

[Relationship of changes in basement membrane of microvessels after cerebral ischemia/reperfusion and plasminogen activator system in aged rats].

OBJECTIVE: To study the relationship of changes in basement membrane of cerebral micro-vessels and plasminogen activator system after cerebral ischemia/reperfusion (I/R) injury in aged rats. METHODS: Middle cerebral artery occlusion (MCAO) was produced by the introduction of a thread. Rats were divided randomly into sham-operation group with young rats (cerebral ischemia 3 hours and I/R 6, 12, 24, 72, 144 hours groups), sham-operation group and I/R groups in aged rats (cerebral ischemia 3 hours and I/R 6, 12, 24, 72, 144 hours groups). Immunohistochemical technique, zymogram analysis, and reverse zymogram analysis were used to study changes in basement membrane structure of cerebral-cortex microvessel, type IV collagen (Col IV) and laminin (LN) contents, and plasminogen activator system in every group. RESULTS: With the increase of age, Col IV and LN contents of the microvessel basement membrane increased. With prolongation of I/R, the contents of Col IV and LN decreased in both young and aged rats, while the contents of tissue plasminogen activator (t-PA), urokinase plasminogen (u-PA) and plasminogen activator inhibitor (PAI-1) expression increased at the beginning and decreased subsequently. Compared with young groups, Col IV (ischemia 3 hours-I/R 12 hours), LN (ischemia 3 hours-I/R 24 hours), t-PA (I/R 6-24 hours) and u-PA (I/R 12-144 hours) expression levels were higher in aged rats, but PAI-1 (I/R 12 and 24 hours) expression was lower. In addition, changes in PAI-1 contents as determined with reverse zymogram analysis method coincided with its immunoexpression. CONCLUSION: With the increase of age, alterations in constituents of cerebro-microvessel basement membrane (Col IV and LN) increased. Injury to cerebro-microvessel basement membrane resulted in more serious changes in aged rats compared with the young rats. Changes in cerebro-microvessel basement membrane after I/R injury in the aged SD rats is related to change in plasminogen activator system.