[Ligustrazine alleviates the tissue injury of the submandibular glands by enhanceing the antioxidant and anti-inflammatory effects in diabetic rats].

Objective To study the effects of ligustrazine on the expression of heme oxygenase 1 (HO-1)/carbon monoxide (CO), inducible nitric oxide synthase (iNOS)/nitric oxide (NO) and tumor necrosis factor α (TNF-α) in the submandibular glands (SMGs) of diabetic rats and their implications. Methods Thirty SD rats were randomly divided into control group, diabetic mellitus (DM) group and ligustrazine group, with 10 rats in each group. The control group received no treatment. The rats of the DM group and ligustrazine group were fed with high-fat diet for 8 weeks, and then a single intraperitoneal injection of 20 g/L streptozotocin (STZ) (35 mg/kg) was used to establish the model of type 2 diabetes mellitus (T2DM). The rats in both groups were fasted for 12 hours, and blood samples were collected from the tail vein for fasting blood glucose (FBG) 1 week after the injection. Rats with FBG values > 7 mmol/L were adopted as the standard for the successful establishment of T2DM rat model. After establishment of the diabetic rat model, the rats in the ligustrazine group were treated with ligustrazine [150 mg/(kg.d)] for 8 weeks, and all rats were fed continuously with ordinary diet during the experiment. The content of FBG, triglyceride (TG) and cholesterol (TC) in each group were measured by automatic biochemical analyzer. The content of arterial blood CO was determined by blood gas analysis. The content of malondialdehyde (MAD) and superoxide dismutase (SOD) in the SMGs, serum NO were measured by colorimetriy. HE staining was used to detect histopathological changes in the SMGs of rats. Immunocytochemistry was used to detecr the expression of HO-1, iNOS and TNF-α in the SMGs. Computer image analysis was used to detect the average absorbance (A) values of HO-1, iNOS and TNF-α expression. Results HE staining showed the acinus was mildly atrophied and the acinar cells were rearranged in an irregular way in the DM group. The morphology of ligustrazine-administered diabetic SMGs was similar to that of the control group. Compared with the control group, FBG, TG and TC in the DM group and ligustrazine group significantly increased; the content of CO and SOD significantly decreased; NO and MDA significantly increased; the expression of HO-1 was significantly down-regulated; and iNOS and TNF-α were significantly up-regulated. Compared with DM group, FBG in the ligustrazine group was significantly reduced; the content of CO and SOD were significantly elevated; NO and MDA were significantly inhibited; the expression of HO-1 was significantly raised; iNOS and TNF-α were significantly inhibited. Conclusion Ligustrazine can up-regulate the expression of HO-1/CO and down-regulate the expression of iNOS/NO and TNF-α, which suggests that ligustrazine plays a protective role in the SMGs by enhancing the antioxidant and anti-inflammatory ability of diabetic rats.

Insulin on changes in expressions of aquaporin-1, aquaporin-5, and aquaporin-8 in submandibular salivary glands of rats with Streptozotocin-induced diabetes.

OBJECTIVE: This study aimed to explore the relationship between diabetic xerostomia and changes in aquaporin-1 (AQP1), aquaporin-5 (AQP5), and aquaporin-8 (AQP8) expression in the submandibular glands (SMGs), to further study the pathogenesis of diabetic xerostomia and to observe the therapeutic effect of insulin (INS). METHODS: Thirty SD rats were randomized equally into 3 groups: control group, diabetic model (DM) group and insulin (INS) group (n=10, respectively). The control group received no treatment. DM group and INS group were induced by a high-fat diet and streptozotocin intraperitoneal injection. After establishment of a diabetic rat model, the rats in INS group were treated with insulin. Then all rats were fed continuously with ordinary diet for 2 months. H&E staining was used to describe morphologic changes in the SMGs of rats. Immunohistochemistry was used to analyze the expressions and localization of AQP1, AQP5, and AQP8 in the SMGs. Computer image analysis was used to detect the mean optical density (MOD) values of AQP1, AQP5, and AQP8 expression, and changes in the diameters of acini and ducts. RESULTS: The acini were mildly atrophied and the acinar cells were rearranged in an irregular way. The morphology of insulin-administered diabetic SMGs was similar to that of the control group. The acinar average circumference and GCT average diameter in DM group were significantly reduced (P<0.05). The acinar average circumference and GCT average diameter of INS group were significantly increased (P<0.05). The expressions of AQP1, AQP5, and AQP8 were significantly reduced in DM group (P<0.05). The expressions of AQP1, AQP5, and AQP8 in INS group were significantly increased (P<0.05). CONCLUSION: The decreased expressions of AQP1, AQP5, and AQP8 led to decreased salivary secretion of SMGs in diabetic rats, which may be involved in the pathogenesis of diabetic xerostomia. Insulin could up-regulate the expressions of AQP1, AQP5 and AQP8, and play a protective role in the secretory function of diabetic SMGs.

Malignant Gastrointestinal Neuroectodermal Tumors: Clinicopathological and Prognostic Features of 96 Patients.

PURPOSE: Gastrointestinal neuroectodermal tumors (GNETs) are uncommon malignant tumors derived from ectodermal primitive neural cells. PATIENTS AND METHODS: We retrospectively analyzed 2 GNET cases at our hospital and the remaining 94 cases in the literature to determine clinicopathological prognostic factors. RESULTS: The patients had a mean age of 36 years and a median tumor size of 4.5 cm. A total of 67.0% of the tumors were located in the small intestine, and 76.4% of the patients presented recurrence or metastasis. There was a significant difference in sex and presence of osteoclast-like cells (P<0.01). Microscopically, most cells were round or short spindle-like in shape, with weak eosinophilic or clear cytoplasm. Neoplastic cells were always arranged in solid sheets, nests, and pseudoalveoli. Immunohistochemistry showed strong, diffuse S100 and SOX10 expression, with a complete absence of HMB45 and Melan-A expression. A total of 72.9% of the cases revealed genetic EWSR1 recombination, including our 2 cases. The median time to death and first metastasis was 61 months and 12 months, respectively. K-M analysis showed a great difference in survival according to lymph node invasion or distant metastasis (M+N), independent lymph node metastasis (N), lower histological grades (G2), and aggressive chemoradiotherapy (P=0.026, P=0.027, P=0.039 and P=0.037). However, independent T, independent M, and postoperative routine adjuvant therapy showed no statistical influence on overall survival or disease-free survival. CONCLUSION: GNET is a new entity distinct in its clinical, morphological, immunochemical, and genetic features. Radical excision, close follow-up and adjuvant therapy may be effective for prolonged survival.