Objective To investigate the role of AT1 receptor autoantibody (AT1-AA) in the inhibitory action of irbesartan on endoplasmic reticulum stress (ERS)-related apoptotic signals in rat kidney with diabetic nephropathy (DN).Methods DN model rats were induced by high-sugar and high-fat diet plus intraperitoneal injection of streptozotocin,and the serum level of AT1-AA was detected by ELISA.These DN rats with positive or negative AT1-AA were divided into DN group and irbesartan treated group.After 4 weeks of irbesartan treatment,TUNEL staining was used to detect renal cell apoptosis.The protein and mRNA expressions of ERS chaperone protein glucose-regulated protein 78 (GRP78) and ERS-associated apoptosis proteins were determined by Western blot and RT-PCR.Results Compared with NC group,the apoptosis rate of renal cells in DN group was obviously increased,along with the increased expressions of GRP78,C/EBP homology protein (CHOP),phosphorylated c-Jun N-terminal kinase (JNK),and Caspase12 protein and mRNA (all P＜0.01).The cell apoptosis and protein and mRNA levels of these genes were significantly decreased after irbesartan treatment (all P＜ 0.01),especially in AT1-AA positive DN rats(all P＜0.05).The renal cell apoptosis rate,and protein and mRNA levels of these four genes in AT1-AA positive DN group were much greater than those in AT1-AA negative DN group (all P＜0.05).Conclusions AT1-AA may be involved in ERS-related cell apoptosis in the kidney of DN rats,and play a role in irbesartan-improved renal function via inhibiting ERS-associated CHOP-JNK-Caspase12 apoptotic signals and renal cell apoptosis.

Objective To observe the effects of doxazosin on the expression of type Ⅰ and type Ⅲ collagen fiber in autoantibodies against α1-adrenergic receptors (α1-AA) positive diabetic rats,and to investigate the protective mechanism of doxazosin on cardiomyopathy of diabetic rats.Methods After establishment of diabetes model with streptozocin,diabetic rats were randomly divided into diabetic group (group A,n =10),doxazosin treated group (group B,n =10),α1-AA mediated group (group C,n =8),α1-AA plus doxazosin treated group (group D,n =8).Group C and group D were injected α1-AA (100 μg/100 g) by caudal vein at 0,4,8,12,and 16 weeks.Doxazosin (0.36 mg · kg-1 · d-1) was administered by lavage for 16 weeks in group B and group D,and other groups were given the same volume of saline every day.Expressions of type Ⅰ and type Ⅲ collagen fibers in myocardium of left ventricle were detected by immunohistochemical staining.Pathological changes in the myocardium were observed by both light and electron microscopes.Changes in collagen fiber in myocardium were detected by Van Gieson staining.Results Among various groups,there was no significant difference in blood glucose levels (P ＞ 0.05).After the intervention of doxazosin,body weight in group B and group D was greater than that of group A and group C (P＜0.05 or P＜0.01).Expression of type Ⅰ and type Ⅲ collagen fibers in myocardium in group D was lower than that in group C (P＜0.05).Expression of type Ⅰ and type Ⅲ collagen fibers in group B was lower than that in group A (P＜0.05) as well.Myocardial pathological changes in group C were most serious,showing reduced mitochondrial,vacuolar degeneration,and interstitial collagen hyperplasia.Cardiomyopathy in group D and group B was less marked as compared with that in group C and group A,respectively.Myocardial collagen fiber in group C was significantly increased and showed poor alignment.Compared with group C,myocardial collagen deposition in group D was obviously reduced.Conclusions Doxazosin may suppress type Ⅰ and type Ⅲ collagen expressions in myocardium of α1-AA mediated diabetic rats,resulting in alleviation of myocardial fibrosis and protection of myocardium in diabetic rats.

Objective: To establish the quality standards for Zhichuang capsules. Methods: Rhubarb, Mahonia, Angelica and Borneol in the formula were identified by TLC, the content of emodin and chrysophanol from Rhubarb in Zhichuang capsules were deter-mined by HPLC. Results: The qualitative identification was easy to operate with good specificity. The linearity was good ( r =0. 999 9) within the range of 25.8-516.0ng and the average recovery was 97.31%(RSD=0.69%,n=6)for emodin, the linearity was good (r=1.000 0) within the range of 51.1-1 022.0ng and the average recovery was 97.63%(RSD=0.72%,n=6)for Chry-sophanol. Conclusion:The method is reliable and accurate, which can be applied as a quality control method of Zhichuang capsules.

BACKGROUND: Pathological scars are a disorder that can lead to various cosmetic, psychological, and functional problems, and no effective assessment methods are currently available. Assessment and treatment of pathological scars are based on cutaneous manifestations. A two-photon microscope (TPM) with the potential for real-time non-invasive assessment may help determine the under-surface pathophysiological conditions in vivo . This study used a portable handheld TPM to image epidermal cells and dermal collagen structures in pathological scars and normal skin in vivo to evaluate the effectiveness of treatment in scar patients. METHODS: Fifteen patients with pathological scars and three healthy controls were recruited. Imaging was performed using a portable handheld TPM. Five indexes were extracted from two dimensional (2D) and three dimensional (3D) perspectives, including collagen depth, dermo-epidermal junction (DEJ) contour ratio, thickness, orientation, and occupation (proportion of collagen fibers in the field of view) of collagen. Two depth-dependent indexes were computed through the 3D second harmonic generation image and three morphology-related indexes from the 2D images. We assessed index differences between scar and normal skin and changes before and after treatment. RESULTS: Pathological scars and normal skin differed markedly regarding the epidermal morphological structure and the spectral characteristics of collagen fibers. Five indexes were employed to distinguish between normal skin and scar tissue. Statistically significant differences were found in average depth ( t = 9.917, P <0.001), thickness ( t = 4.037, P <0.001), occupation ( t = 2.169, P <0.050), orientation of collagen ( t = 3.669, P <0.001), and the DEJ contour ratio ( t = 5.105, P <0.001). CONCLUSIONS Use of portable handheld TPM can distinguish collagen from skin tissues; thus, it is more suitable for scar imaging than reflectance confocal microscopy. Thus, a TPM may be an auxiliary tool for scar treatment selection and assessing treatment efficacy.
Humans ; Cicatrix/diagnostic imaging* ; Skin/pathology* ; Collagen ; Imaging, Three-Dimensional/methods*