[Intervention of Tibetan medicine--twenty wei chenxiang pill on elevation of hypoxic pulmonary arterial pressure in rats].

OBJECTIVE: To investigate the role of Tibetan medicine-Twenty Wei Chenxiang Pill interfering with serum ET-1 level, in order to confirm that ET-1 is involved to the pathogenesis of hypoxic pulmonary hypertension. METHODS: 165 Wistar rats were randomly divided into high altitude control group,Tibetan medicine-Twenty Wei Chenxiang Pill group and plain control group. The physiological signal acquisition system was used to record pulmonary arterial pressure, and RV/(LV + S) ratio were caculated. Serum HIF-1alpha and ET-1 protein levels were determined by the method of ELISA, and ETA protein levels in lung tissue were determined by Western Blot method. RESULTS: Compared with the high altitude group,in the rats of Tibetan medicine-Twenty Wei Chenxiang Pill group,the pulmonary arterial pressure decreased significantly from the seventh day and the seventh day (P < 0.01), the RV/(LV + S) ratio and serum HIF-1alpha levels decreased significantly from the third day (P < 0.05 or P < 0.01), the serum ET-1 levels decreased significantly from the third day (P < 0.05 or P < 0.01), and the expression of ETA protein decreased significantly from the beginning (P < 0.01 or P < 0.001). CONCLUSION: ET-1 is one of the important factors causing pulmonary artery pressure increasing and right ventricular wall thickening, which plays a role in hypoxic pulmonary artery only involved in the early period hypoxia, but not in the later period. Tibetan medicine--twenty Wei Chenxiang Pill can prevent the pulmonary artery hypertension and the right ventricular wall thickening in rats, and its mechanism may be related to the direct inhibition of ET-1 and protein levels of ETA or the indirect downregulation of ET-1 level and ETA through inhibition of HIF-la level.

[Neurological adaptations to hypoxia in Tibetan antelope (Pantholops hodgsonii) with a view of molecular biology of respiratory globin-neuroglobin].

Neuroglobin (Ngb) is a respiratory protein that is preferentially expressed in brain of mouse and man. In this article, Tibetan antelope, living at altitude of 3 000-5 000 m for millions of years, was selected as the model of hypoxia-tolerant adaptation species. Using reverse transcription polymerase chain reaction (RT-PCR) and Western blot techniques, expression of Ngb gene was amplified and analyzed in antelope brain tissue. Our results showed that Ngb homology protein in Tibetan antelope was identified with more sequence similarity with cattle (96%), sheep (95%), and human (95%). We detected that there were some mutations occurred in the Open Reading Frame of Ngb in Tibetan antelope compared with sheep. Phylogenetic analysis of Ngb chain showed that it was closer to cattle than the others. This study suggests possible roles of central nervous system enriched Ngb in adaptation of Tibetan antelope to extremely high altitude.

[Energy power in mountains: difference in metabolism pattern results in different adaption traits in Tibetans].

Energy metabolism plays an important role in life survival for species living in high altitude hypoxia condition. Air-breathing organisms require oxygen to create energy. Tibetans are the well-adapted highlanders in Qinghai-Tibetan Plateau. It was thought that different metabolic approaches could lead to different adaptation traits to high altitude hypoxia. Recently identified hypoxia inducible factors pathway regulators, endothelial PAS domain protein1 (EPAS1)/HIF-2a and PPARA, were involved in decreasing hemoglobin concentrations in Tibetans. Because EPAS1 and PPARA also modulated the energy metabolism during hypoxia, we hypothesized that positive selected EPAS1 and PPARA genes were also involved in unique energy metabolisms in Tibetans. In this brief review, we take a look into genetic determinations to energy metabolisms for hypoxia adaptations traits in Tibetans and mal-adaptive conditions such as high altitude diseases.

[The dynamic changing profiles of peripheral white blood cell telomere length in populations of different ages living at different altitude areas].

OBJECTIVE: To investigate the relationship between the length of telomere DNA and age at different altitude areas. METHODS: All 172 peripheral blood samples were randomly selected from healthy individuals of different ages from 25 to 65 years old. High altitude group (47 males, 48 females) living at an altitude of 4380 m (HA group), sea level group (39 males, 38 females) living at an altitude of 43 m (SL group). The terminal restriction fragment (TRF) length of telomere DNA was measured by Southern blotting analysis. The plasma levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were assayed. RESULTS: Average TRF lengths of males and females in HA groups were 10.45 +/- 1.35 and 10.50 +/- 1.45. Average TRF lengths of males and females in SL groups were 11.29 +/- 1.10 and 11.31 +/- 1.13. A negative correlation was shown between the average TRF length and age of males in two groups (P < 0.01). This was also the case for females. ANOVA test was used to analyze the difference between TRF length and gender at different ages (P < 0.001). It was shown that there was significant difference in TRF length between the male (25 years old and 55 years old) and female (25 years old and 55 years old) in two groups at different ages (P < 0.05). The plasma levels of SOD and MDA were significant different between HA groups and SL groups (25-44 years old groups/45-65 years old groups) (P < 0.05). CONCLUSION: Obviously shortening of telomere was observed by increasing of ages in high altitude groups. There was a negative correlation between the length of telomere DNA and ages. Telomere shortening became more obviously in high altitude group than in sea level group in keeping with the age increases.

[Cloning and homologous analysis of coding region of alpha-globin gene from Tibetan antelope].

AIM: To clone and analyze the encoding region of alpha-globin gene from Tibetan antelope. METHODS: Total RNA was isolated from an adolescent Tibetan antelope liver, and Tibetan antelope alpha-globin gene was amplified by RT-PCR. The PCR product was cloned into pGEM-T vector and sequenced. Nucleotide sequences were compared with GenBank data by Blast method. RESULTS: The encoding region of alpha-globin gene of Tibetan antelope was obtained and deposited in GenBank as accession number DQ650713. Compared with sheep alpha-chain, alterations in important regions could be noted: a132 Asn-->Ser, a134 Ser-->Gly; but 19 differences were detected when compared with that of human. Phylogenetic analysis showed that the encoding region of alpha-globin gene of Tibetan antelope was most likely close to that of sheep and goat. CONCLUSION: The encoding region of gene Tibetan antelope alpha-globin gene is successfully cloned, which provides basic information for elucidating the possible role of hemoglobin in high altitude adaptation of Tibetan antelope.

[Electrophysiological study on rat conduit pulmonary artery smooth muscle cells under normoxia and acute hypoxia].

The present study was designed to investigate the electrophysiological characteristics of rat conduit pulmonary artery smooth muscle cells (PASMCs) and the response to acute hypoxia. PASMCs of the 1st to 2nd order branches in the conduit pulmonary arteries were obtained by enzymatic isolation. The PASMCs were divided into acute hypoxia preconditioned group and normoxia group. Hypoxia solutions were achieved by bubbling with 5% CO2 plus 95% N2 for at least 30 min before cell perfusion. Potassium currents were compared between these two groups using whole-cell patch clamp technique. The total outward current of PASMCs was measured under normoxia condition when iBTX [specific blocking agent of large conductance Ca-activated K(+) (BK(Ca)) channel] and 4-AP [specific blocking agent of delayed rectifier K(+) (K(DR)) channel] were added consequently into bath solution. PASMCs were classified into three types according to their size, shape and electrophysiological characteristics. Type I cells are the smallest with spindle shape, smooth surface and discrete perinuclear bulge. Type II cells show the biggest size with banana-like appearance. Type III cells have the similar size with type I, and present intermediary shape between type I and type II. iBTX had little effect on the total outward current in type I cells, while 4-AP almost completely blocked it. Most of the total outward current in type II cells was inhibited by iBTX, and the remaining was sensitive to 4-AP. In type III cells, the total outward current was sensitive to both iBTX and 4-AP. Acute hypoxia reduced the current in all three types of cells: (1614.8+/-62.5) pA to (892.4+/-33.6) pA for type I cells (P<0.01); (438.3+/-42.8) pA to (277.5+/-44.7) pA for type II cells (P<0.01); (1 042.0+/-37.2) pA to (613.6+/-23.8) pA for type III (P<0.01), and raised the resting membrane potentials (E(m)) in all these three types of cells: (-41.6+/-1.6) mV to (-18.6+/-1.5) mV (P<0.01), (-42.3+/-3.8) mV to (-30.6+/-3.0) mV (P<0.01), (-43.3+/-1.6) mV to (-28.4+/-1.4) mV (P<0.01), for type I, II, III cells, respectively. These results suggest that acute hypoxia suppresses the potassium current and improves the E(m) in PASMCs. These effects may be involved in the modulation of constriction/relaxation of conduit artery under acute hypoxia. Different distribution of K(DR) and BK(Ca) channels in these three types of PASMCs might account for their different constriction/relaxation response to acute hypoxia.