Protective effects of choline against hypoxia-induced injuries of vessels and endothelial cells.

The current study aimed to lay a theoretical foundation for further development of choline as an anti-hypoxia damage drug. Wild-type, 3- to 5-month-old male Sprague-Dawley rats, weighing 180-220 g, were used in this study. The rats were randomly divided into a normoxic control group (n=16) and a chronic intermittent hypoxia (CIH) group (n=16). The effects of CIH on acetylcholine (ACh)-mediated endothelium-dependent vasodilatation in the rat cerebral basilar arterioles and mesenteric arterioles, as well as the protective effects of choline on the arterioles damaged by hypoxia were observed. Moreover, the effects of choline on endothelial cell proliferation during hypoxia were observed, and choline's functional mechanism further explored. The ACh-mediated vasodilatation of rat cerebral basilar and mesenteric arterioles significantly reduced during hypoxia (P<0.01). Choline significantly increased dilation in the rat cerebral basilar (P<0.01) and mesenteric arterioles (P<0.05) damaged by CIH compared with those in the control group. In addition, under hypoxic conditions, choline significantly promoted the proliferation of rat aortic endothelial cells (P<0.05) and significantly reduced lactate dehydrogenase activity in the cell culture supernatant in vitro (P<0.05). Furthermore, the effect of choline could be related to its ability to significantly increase the secretion of vascular endothelial growth factor (P<0.01) and activation of α7 non-neuronal nicotinic acetylcholine receptors under hypoxia (P<0.01). This study demonstrated that choline could have protective effects against hypoxic injuries.

Diazoxide protects rat vascular endothelial cells against hypoxia and cold-induced damage.

The present study aimed to examine the effects of hypoxia and cold on vascular endothelial cells (VECs), as well as the protective ability of novel VECs-protective drugs against these injuries. A rat model simulating exposure to hypoxia and cold at high altitude environments was established. Based on these animal experiments, rat aortic VECs were established as injury models and exposed to hypoxia and/or adrenaline (ADR) in vitro. The results revealed that hypoxia significantly altered the levels of nitric oxide and vascular endothelial growth factor, while the cold temperature significantly increased the release of ADR and noradrenaline. Exposure to hypoxia combined with cold temperature significantly affected all these indices. In vitro experiments demonstrated that hypoxia, ADR (which was used to simulate cold in the animal experiments) and the combination of the two factors resulted in damage to the VECs and endothelial dysfunction. In addition, the results also showed that diazoxide, a highly selective mitoKATP opener, protected VECs against these injuries. In conclusion, hypoxia and cold temperature induced endothelial cell dysfunction and endocrine disorders, respectively. Improving endothelial function using diazoxide may be an effective therapeutic strategy in patients with altitude-associated disorders. However, the potential for clinical application requires further study.

The physiological effects of resveratrol and its potential application in high altitude medicine.

Resveratrol, as a natural polyphenolic compound, has a wide range of beneficial effects, which includes anti-tumor, cardiovascular protection, anti-oxidant and estrogen-like effects, and so on. Its various physiological properties are closely related to the therapeutic principle for prevention and treatment of high altitude hypoxia injury. Resveratrol may play an important role in relieving or curing high altitude diseases, especially high altitude polycythemia(HAPC). However, the literature about study and application of resveratrol in plateau medicine field is rarely reported up to now. In this review, we summarized the physiological effects of resveratrol, discussed the possible main principle of resveratrol for HAPC therapy, and looked forward to resveratrol's perspective or potential application in high altitude medicine.

A rat model of high altitude polycythemia rapidly established by hypobaric hypoxia exposure.

OBJECTIVE: To investigate the effects of simple hypobaric hypoxia on parameters of hematology and blood rheology in order to establish a rat model of simulated high altitude polycythemia (HAPC) for the study of pathophysiologic mechanisms and medical prevention and treatment of HAPC. METHODS: Forty-eight male Wistar rats were randomly divided into three normal control groups and three hypoxia model groups. Normal control group rats were bred in normoxia conditions, and hypoxia group rats were subjected to hypoxic exposure for 8 hours per day at simulated 5 500 m high altitude in a hypobaric chamber. After hypoxic exposure for 2, 4, 12 weeks, one group of normal control and hypoxia model rats were killed and blood was collected, respectively. Then parameters of erythrocyte and blood rheology were examined. RESULTS: Mucous membrane of hypoxia model rats showed obviously cyanosis after 2 weeks hypoxic exposure. Hemoglobin concentration of hypoxia model rats were beyond 210 g/L after 2 weeks, 4 weeks and 12 weeks hypoxia exposure and significantly increased than that of normal control rats respectively. Besides, RBC counts, hematocrit, whole blood viscosity, erythrocyte aggregation index of hypoxia model rats were all notably higher than those of normal control rats respectively. CONCLUSION: A rat model of high altitude polycythemia can be rapidly established by hypobaric hypoxia exposure at simulated 5 500 m high altitude for 8 hours daily.

[Study on leptin enhancing collagen systhesis in wounded rats].

OBJECTIVE: To investigate the effect of leptin on collagen systhesis in wounded rats. METHODS: Thirty male Wistar rats, weight (180 +/- 20)g, were randomly divided into three groups (n = 10) by weight: normal depilation group, wound control group and leptin treatment group and ten rats were included in each group. A full-thickness defect measuring 2 x 2.5 cm was made in the back of rats in wound control group and leptin treatment group. Each wound in rats of leptin treatment group was applied topically with 0.1 ml leptin solution (2.0 microg leptin), daily for 7 days and that of wound control group with equivalent saline solution. All rats were killed and then granulation tissues samples and skin were collected to examine the synthesis of collagen. RESULTS: Hydroxyproline content in granulation tissues of in leptin treatment group (33.92 +/- 3.09) mg/g were significantly increased than those in control group (29.55 +/- 3.59 mg/g, P < 0.05). The mRNA expressions of collagen I and III were significantly enhanced in leptin treatment group (0.96 +/- 0.09, 0.09 +/- 0.06) than those in control group (0.80 +/- 0.03, 0.08 +/- 0.03). The levels of type I and III collagen were significantly increased in leptin treatment group than those in control group. CONCLUSION: Leptin applied topically can accelerate wound healing through enhancing gene expression of type I and III collagen and synthesis of collagen in wound tissue.

[Effects of soybean isoflavones on the cell cycles, the cell apoptosis and the proliferation of spleen in radiated mice].

AIM: To study effect of soybean isoflavones (SI) on spleen in radiated mice. METHODS: 90 male mice were randomly divided into control group, radiated group, radiated plus 0.5% dose SI group. After 2-week feeding, the mice received 4.0 Gy 137Cs gamma-radiation, the cell cycles, cell apoptosis and proliferation on the spleen and the spleen index were observed in radiated after 12 h, 24 h, 1 week and 2 weeks. RESULTS: After the mice were radiated, the spleen were significantly atrophy, the rate of the cell apoptosis and the cell cycles of G0-G1 phase in splenocytes were significantly increased (P < 0.01), the cell cycles rate of S phase and the proliferation index were significantly decreased in spleen (P < 0.05). Compared with radiated group, the spleen atrophy and the rate of the cell cycles of G0-G1 phase were significantly decreased (P < 0.05), and the cell cycles of G2-M phase and the proliferation index were significantly increased (P < 0.05) in the mice supplied 0.5% soybean isoflavones. CONCLUSION: The soybean isoflavones could significantly increase spleen radioprotective effect in mice.