According to the statistics of the World Health Organization (WHO), the total area of the global plateau is approximately 30 million square kilometres, and more than 140 million people live in plateau areas that are greater than 2500 metres above sea level, of which 60 million live in plateau areas of China [9]. The plateau area is characterized by low pressure, low oxygen, low humidity, a large temperature difference between day and night, and strong ultraviolet radiation [1–2], among which low pressure and low oxygen are the most important characteristics that affect the health of local people and restrict local development and long-term economic development. As a special ecological environment system, the plateau environment is highly valued by all countries for special political, social, economic, military and other reasons. People who migrate to or live in high-altitude areas are prone to acute or chronic high-altitude disease; multiple systems of the body are affected, and blood indicators change. At present, the pathogenesis of this disease has not been fully clarified [3–4]. In addition, most of the experimental studies on animals at high altitude are carried out in simulated spaces such as low-pressure and hypoxic cabins, which cannot objectively and truly reflect the physiological and pathological changes of the subjects at high altitude. Based on this, this study conducted research on SD rats in a real low-pressure and hypoxic environment at high altitude, including assessment of red blood cells, white blood cells, platelets and blood biochemical indicators, to comprehensively analyse the changes in blood indices in rats in a chronic high-altitude hypobaric hypoxic environment.
Red blood cells are blood cells with the largest number in the blood. They are also the main medium for vertebrates to transport oxygen through the blood. At the same time, they also have immune functions [10]. Red blood cells contain haemoglobin, which can combine with oxygen in the air. Therefore, red blood cells can transport oxygen inhaled into the alveoli to the tissues through haemoglobin, and part of the carbon dioxide generated by metabolism in the tissues is also transported to the lungs through red blood cells for the exchange of gas with oxygen outside the alveoli and the expulsion of carbon dioxide from the body [11–12]. Table 1 (Fig. 1A-F)shows that RBCs in the plateau group were higher than those in the plains group, but there was no significant difference between the two groups (P > 0.05). Compared with the plains group, HGB, MCV, MCH, MCHC and RDW in the plateau group were significantly higher (P < 0.05). These results show that the blood composition of rats in the plateau group has changed, with increases in HGB, the percentage of red blood cells in a certain volume of whole blood, the volumes of the individual red blood cells, the average amount of haemoglobin contained in each red blood cell, the average grams of haemoglobin contained in each litre of blood cells, and the volume heterogeneity of the peripheral red blood cells. The possible reasons may be the low-pressure and hypoxic environment on the plateau. The decrease in oxygen content in the arterial blood of the body results in a high expression of erythropoietin and then an increase in haemoglobin content to improve the oxygen-carrying capacity. However, in this study, the number of red blood cells per unit volume of blood in the plateau group was slightly larger than that in the plains group, and the difference was not statistically significant, which was inconsistent with the literature reports. On the one hand, this may be due to the small sample size included in this study; on the other hand, it may be because the oxygen supply needs of rats can be met through the adjustment of HGB after environmental adaptation and that the number of red blood cells per unit volume of blood can be no different. In the future, we will continue to increase the sample size and conduct a comparative study at multiple altitudes.
White blood cells are a very important kind of blood cell in the blood. White blood cells are the "guardians" of the human body in the fight against disease. When bacteria invade the human body, white blood cells can pass through the capillary wall through deformation, concentrate on the invasion site of bacteria, and surround and engulf the bacteria [13–14]. Different kinds of white blood cells participate in the body's defence response in different ways [15–16]. Table 2 (Fig. 2A-F)shows that compared with the plains group, WBC, LYMP, EO, LYMP% and EO% in the plateau group decreased significantly (P < 0.05), and ANC% increased significantly (P < 0.05). The ANC, MONO and BASO in the plateau group were lower than those in the plains group, but the difference was not statistically significant (P > 0.05). The MONO% and BASO% in the plateau group were higher than those in the plains group, and the difference was not statistically significant (P > 0.05). The white blood cells in the blood components of rats at high altitude changed; there were increases in the number of white blood cells, the absolute number of lymphocytes, the percentage of lymphocytes, the absolute number of eosinophils, and the percentage of eosinophils and a decrease in the percentage of neutrophils. The changes in leukocyte-related indicators in the high-altitude group suggest that the body's resistance to disease is reduced in the low-pressure and hypoxic environment at high altitudes. Whether this is related to the occurrence of acute and chronic high-altitude disease remains to be further studied.
Platelets are small pieces of cytoplasm detached from the cytoplasm of mature megakaryocytes in the bone marrow [17]. The main function of platelets is to coagulate and stop bleeding and to repair damaged blood vessels [18–19]. Table 3 (Fig. 3A-D) shows that compared with the plains group, PLT in the plateau group decreased significantly (P < 0.05), PDW, MRV, and P-LCR increased significantly (P < 0.05), and PCT in the plateau group decreased compared with the plains group, but the difference was not statistically significant (P > 0.05). These results show that the composition of platelets in the blood of rats at high altitude changes, with a decrease in platelet count and increases in the distribution of platelet size in the blood, the average platelet volume, and the percentage of large platelets in total blood platelets. The changes in platelet-related indicators suggest that coagulation and haemostasis functions may be affected in the low-pressure and hypoxic environment at high altitude, with a risk of bleeding.
In addition to blood cells, there are many different substances in the blood. Determination of the content of various ions, sugars, lipids, proteins, enzymes, hormones and various metabolites of the body in the blood is known as blood biochemical examination. Among the blood biochemical indicators, ALT has been recommended by the World Health Organization as the most sensitive indicator for damage to liver function [20]. AST is another indicator for liver function and is generally used to check whether the liver tissue is damaged [21]. The determination of serum total bilirubin is an important test for examination of liver and biliary function. Total bilirubin (TBil) is the sum of direct bilirubin (DBIL) and indirect bilirubin (IBIL). The liver plays an important role in the metabolism of bilirubin [22]. Creatine kinase mainly exists in the cytoplasm and mitochondria. It is an important kinase directly related to energy transfer, muscle contraction and ATP regeneration in cells. The determination of creatine kinase activity can be used for the diagnosis of skeletal muscle diseases and myocardial diseases [23]. LDH is a glycolytic enzyme that exists in the cytoplasm of all tissues and cells of the body, and the LDH content in the kidney is higher [24]. Table 4 (Fig. 4A-E)shows that compared with the plains group, ALT, DBIL, UCr and TC in the plateau group decreased, with no statistically significant difference (P > 0.05); ALT/AST and ALP in the plateau group increased, with no statistically significant difference (P > 0.05); AST, TBIL, IBIL and LDH in the plateau group decreased significantly (P < 0.05); and CK in the plateau group increased significantly (P < 0.05). These results show that the biochemical indices in the blood of rats at high altitude were partially changed; there were decreases in aspartate aminotransferase, total bilirubin, indirect bilirubin, and lactate dehydrogenase and an increase in creatine kinase. It is speculated that the liver function, renal function, heart function and skeletal muscle energy metabolism of rats may be affected in a high-altitude hypobaric hypoxic environment.
Limitations
The disadvantage of this study is that the sample size included was small and will be further increased in the future. Only the changes in blood indices of rats in the natural environments of plateaus and plains were studied. In the next step, the changes in blood indices of rats in the natural environment of different altitudes will be further studied.