3. Effects of tongluo recipe on renal expression of Ang II, VEGF, and ERK1/2 in rat models of type 1 diabetes mellitus
Academic Journal of Second Military Medical University 2011;32(10):949-954
Objective To observe the effects of Tongluo recipe on extracellular signal-regulated protein kinase (ERK1/2) pathway in the kidneys of streptozotocin-induced rat models of type 1 diabetes mellitus, andto explore the renoprotective mechanism of Tongluo recipe. Methods Adult male Sprague-Dawley rats were randomly divided into 2 groups: control group (A, n = 10) and experimental group. Rats in the experimental group were induced by intraperitoneal injection of streptozotocin (60 mg/kg body mass), and were randomly subdivided into group B (diabetic control, n = 10), group C (diabetic rats treated with low dose of Tongluo recipe, 0. 5 g/[kg • d], n = 10), group D (diabetic rats treated with medium dose of Tongluo recipe, 1. 0 g/[kg • d], n = 10), group E (diabetic rats treated with high dose of Tongluo recipe,2. 0 g/[kg • d], n = 10) and group F (diabetic rats treated with losartan, 30 mg/[kg • d],n=10). At the end of the 12th week rats were sacrificed, and the serum glucose, triacylglycerol(TG), total cholesterol(Choi), serum creatinine(Scr), urea nitrogen(BUN) in blood, 24-hour urine protein(Upro24), microalbuminuria (MAU), and creatinine in urine(UCR) were examined. The kidney mass/body mass (KM/BM) and creatinine clearance rate (Ccr) were calculated. The left kidneyswere collected, weighed and subjected to H-E staining and PAS staining to observe the pathological changes; serum and renal tissue angiotensin II (Ang II) levels were determined by ELISA; the expression of phosphorylated ERK1/2(p-ERK1/2) was detectedby immunohistochemical staining and vascular endothelial growth factor (VEGF) protein expression was determined by Western blotting analysis. Results Compared with group B, group D had a slighter mesangial proliferation under light microscope. Besides, rats in group D had significantly decreased Ccr, BUN, MAU, and Upro24 in the serum, and decreased Ang II in the serum and renal tissue, and decreased KM/BM, VEGF and p-ERK1/2 levels in renal tissue compared with rats in group B(P<0. 05). The medium dose of Tongluo recipe and losartan showed similar effects in improving the renal function and inhibiting Ang II, VEGF, and p-ERK1/2 expression of diabetic rats. Conclusion The renoprotective effect of Tongluo recipe may be related to inhibition of ERK1/2 cascade pathway by decreasing the expression of Ang II and VEGF.
4. Effects of Tongluo recipe on renal expression of Ang II, VEGF, and ERK1/2 in rat models of type 1 diabetes mellitus
Academic Journal of Second Military Medical University 2011;32(9):949-954
Objective To observe the effects of Tongluo reeipe on extracellular signal-regulated protein kinase (ERK1/2) pathway in the kidneys of streptozotocin-induced rat models of type 1 diabetes mellitus, and to explore the renoprotective mechanism of Tongluo reeipe. Methods Adult male Sprague-Dawley rats were randomly divided into 2 groups: control group (A, n=10) and experimental group. Rats in the experimental group were induced by intraperitoneal injection of streptozotocin (60 mg/kg body mass), and were randomly subdivided into group B (diabetic control, n=10), group C (diabetic rats treated with low dose of Tongluo recipe,0.5g/[kg · d], n=10), group D (diabetic rats treated with medium dose of Tongluo recipe, 1.0g/[kg · d], n=10), group E (diabetic rats treated with high dose of Tongluo recipe, 2.0g/[kg · d], n=10) and group F (diabetic rats treated with losartan, 30 mg/[kg · d],n=10). At the end of the 12th week rats were sacrificed, and the serum glucose, triacylglycerol(TG), total cholesterol(Chol), serum creatinine(Scr), urea nitrogen(BUN) in blood, 24-hour urine protein(Upro24), microalbuminuria (MAU), and creatinine in urine (UCR) were examined. The kidney mass/body mass (KM/BM) and creatinine clearance rate (Ccr) were calculated. The left kídneys were collected, weighed and subjected to H-E staining and PAS staining to observe the pathological changes; serum and renal tissue angiotensin II (Ang II) levels were determined by ELISA; the expressíon of phosphorylated ERK1/2 (p-ERK1/2) was detected by immunohistochemical staining and vascular endothelial growth factor (VEGF) protein expression was determined by Western blotting analysis. Results Compared with group B, group D had a slighter mesangial proliferation under light microscope. Besides, rats in group D had significantly decreased Ccr, BUN, MAU, and Upro24 in the serum, and decreased Ang II in the serum and renal tissue, and decreased KM/BM, VEGF and p-ERK1/2 levels in renal tissue compared with rats in group B(P<0.05). The medium dose of Tongluo recipe and losartan showed similar effects in improving the renal function and inhibiting Ang II, VEGF, and p-ERK1/2 expression of diabetic rats. Conclusion The renoprotective effect of Tongluo recipe may be related to inhibition of ERK1/2 cascade pathway by decreasing the expression of Ang II and VEGF.
5. Effects of Tongluo recipe on renal function and renal expression of CTGF, RAGE, and p-ERK1/2 in rat model of type 1 diabetes mellitus
Academic Journal of Second Military Medical University 2010;31(10):1086-1090
Objective: To observe the effects of Tongluo recipe on the renal expression of connective tissue growth factor (CTGF), advanced glycation end products receptor (RAGE) and phosphorylated extracellular signal regulated kinase (p-ERK1/2) in streptozotocin-induced rat model of type 1 diabetes mellitus, and to explore the mechanism of its renoprotective effect. Methods: Adult male Sprague-Dawley rats, weighing 180-220 g, were randomly divided into 2 groups: control group (A, n=10) and model group (n=50). Rat diabetic model was induced by intraperitoneal injection of streptozotocin (60 mg/kg body weight), and the model rats were randomly subdivided into B group (diabetic control, n=10), C group (diabetic rats treated with low dose of Tongluo recipe, 0.5 g·kg-1·d-1, n=10), D group (diabetic rats treated with medium dose of Tongluo recipe, 1.0 g·kg -1·d-1, n=10), E group (diabetic rats treated with high dose of Tongluo recipe, 2.0 g·kg-1·d-1, n=10), and F group (diabetic rats treated with losartan, 30 g·kg -1·d-1, n=10). At the end of the 12th week the rats were sacrificed and were weighed; the urea nitrogen (BUN) in blood, serum creatinine (Scr), 24 h albumin excretion rate (UPRO24), microalbuminuria (MAU) and creatinine in urine (Ucr) were analyzed by bio-chemical methods. The left kidneys were weighed and the right kidneys were subjected to real-time PCR analysis for the expression of CTGF and RAGE mRNA. Western blotting analysis was used to examine the expression of CTGF, RAGE, p-ERK1/2, and total-ERK1/2 protein expression. Results: The creatinine clearance rate, urea nitrogen, 24 h albumin excretion rate, and microalbuminuria in group D and E were significantly lower than those of group B. And the renal functions of rats in group D and E were improved and the expression of RAGE and CTGF mRNA and protein and p-ERK1/2 protein expression was significantly decreased (P<0.05). Conclusion: Tongluo recipe may exert its renoprotective effect through inhibiting RAGE-ERK1/2-CTGF signal pathway.
6.Clinical and laboratory features of 58 patients with positive cryoglobulin
Wen WEN ; Chun LI ; Rulin JIA ; Zhanguo LI
Chinese Journal of General Practitioners 2016;15(4):286-290
Objective To study the disease spectrum,clinical and lab characteristic of cryoglobulinaemia.Methods The clinical and laboratory data of 58 patients with positive cryoglobulin admitted in Peking University People's Hospital from April 2010 to May 2014 were retrospectively analyzed.Results Among 58 patients,34 were diagnosed as autoimmune disease,8 as infectious disease,4 as hematological disease and 12 as primary cryoglobulinemia.Renal involvement was the most frequent clinical presentation among all cryoglobulin positive patients.Patients with autoimmune disease presented all clinical manifestations related to cryoglobulinaemia.Renal involvement (7/8) was prominent in patients with HBV/HCV infection,while other clinical presentations were rare.Among 4 patients with hematological disease,purpura was presented in 3 cases,renal involvement in 2,arthralgia in 2,fatigue,thrombosis or hyperviscosity was presented in 1 case,respectively;however,none of these patients had elevated rheumatoid factor (RF) level.Renal lesions were the most common reason for patients with primary cryoglobulinaemia to consult doctors,and 5 of them had positive antinuclear antibodies (ANA).Conclusions There is a broad spectrum of disease in cryoglobulinaemia.Multi-system involvement was most common in patients with autoimmune disease.For patients with HBV/HCV infection,extra-hepatic presentations were rare except renal involvement.Hyperviscosity syndrome tended to occur in patients with hematological disease.Since patients with primary cryoglobulinaemia had a relatively high rate of positive antinuclear antibodies,we should keep vigilance at the occurrence of autoimmune disease.
7.Clinical and laboratory features of rheumatic autoimmune disease associated cryoglobulinaemia
Wen WEN ; Chun LI ; Rulin JIA ; Zhanguo LI
Chinese Journal of Rheumatology 2016;(2):100-105
Objective To investigate the clinical and laboratory features of autoimmune disease (AID) associated cryoglobulinaemia. Methods From April 2010 to May 2014, thirty threc patients with AID in Peking University Peopleˊs Hospital were tested positive for cryoglobulin. Their clinical and laboratory features were analyzed retrospectively. T test, Mann-Whitney U test, Chi-squaretest and Fisherˊs exact test were used for statistical analysis. Results Among the 33 patients, 26 were female, 7 were male, the average age was (47 ± 17) years old (range 12-75 years old). The spectrum of autoimmune diseases included, in order, systemic lupus erythematosus (SLE), Sj?grenˊs syndrome (SS), multiple myositis/dermatomyositis, rheumatoid arthritis (RA), systemic sclerosis (SSc), anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, antiphospholipid syndrome and primary biliary cirrhosis. SLE and SS accounted for 84.8% (28/33) in tpatients with cryoglobulinaemia. In patients withSLE, cryoglobulinaemia occurred at 2.0 (1.0-12.0) years after disease onset, and cryoglobulinpositive patients had more frequent renal involvement (71% vs 40%, P=0.004), positive anti-RNP (56% vs21%, P=0.007) and ACL (53% vs 8%, P=0.000). However, among patients with SS, cryoglo-bulinaemia occurred at 11.0 (4.0-18.0) years after disease onset, and cryoglobulin positive patients had higher rheumatoid factors (RF) [1 170 (230.00, 2 800.00) U/ml vs 57.80 (20.00, 230.50) U/ml, U=-0.002, P=0.001], IgM [3.54 (1.83, 4.34) g/L vs 1.17 (0.81, 2.26) g/L , U=0.016, P=0.014] and lower complement C3 [0.58 (0.33, 0.68) g/L vs 0.81 (0.67, 0.98 g/L), U=0.004, P=0.003] and C4 [0.06 (0.03, 0.12) g/L vs 0.16 (0.12, 0.22), U=0.017, P=0.016]. Conclusion Autoimmune disease complicated with cryoglo-bulinaemia is not uncommon in clinical practice, in which SLE and SS account for the leading two causes. Patients with positive anti-RNP and/or ACL are positively associated with cryoglobulinaemia. renal involvement of SLE is increased by the presence of cryoglobulin.
8.Detection of brain energy metabolism changes by proton magnetic resonance spectroscopy in patients with chronic obstructive pulmonary disease
Wen WEN ; Bin SUN ; Deling LIU ; Jia YE ; Guoxiang LAI
Chinese Journal of Geriatrics 2012;31(8):683-685
Objective To study the cerebral energy metabolism changes of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) through hydrogen magnetic resonance spectroscopy examination (1 HMRS ) and its relationship with partial pressure of oxygen / carbon dioxide tension.Methods Totally 13 cases of AECOPD patients and 10 cases of age-matched healthy people underwent HMRS examination.The ratios of n-acetyl-aspartate(NAA)/creatine(Cr),choline (Cho)/Cr,myo-inositol(MI)/Cr of parieto-temporal and occipital areas of brain were detected.Blood gas analysis were also used to detect partial pressure of oxygen (PaO2) and carbon dioxide (PaCO2).Results NAA / Cr of parieto-temporal and occipital areas of brain (1.32±0.12,1.48±0.12) were lower in AECOPD group than those in control group (1.45±0.11,1.58±0.10) (P< 0.05),MI/Cr (0.23±0.07,0.30±0.11) were also decreased compared with control group (0.40±0.14,0.46±0.12) (P< 0.01),while Cho/Cr of parieto -temporal and occipital areas of brain between the AECOPD group and control group showed no significant difference (P>0.05).NAA/Cr of parieto temporal and occipital areas of brain were positively correlated with PaO2 (r=0.46 and 0.44),and MI/Cr of these areas of brain were also positively related with PaO2 (r=0.63 and 0.50),but MI / Cr of parieto tempora was negatively correlated with PaCO2 (r =- 0.472). Conclusions Cerebral metabolite changes may occur in AECOPD patients,and this has relationship with hypoxia and carbon dioxide retention.