Effect of Xuesaitong Combined with Autologous Platelet-rich Gel on Blood Glucose, AT-III, TNF-α and 24-h Urinary Protein Level in Patients with Diabetic Foot

Wei LI, Mei CAO, Hong ZHU

Department of Endocrinology, The Third People’s Hospital of Yunnan Province, Kunming 650011, China

Abstract [Objectives] To investigate the clinical effect of different doses of Xuesaitong combined with autologous platelet-rich gel (APG) on patients with diabetic foot (DF). [Methods] 90 patients with diabetic foot admitted to our hospital from February 2017 to February 2019 were enrolled in the study. According to the random number table method, the subjects were divided into study group A and B and control group C. Group A was given a low dose of Xuesaitong combined with APG, while group B was given high-dose Xuesaitong combined with APG and group C was treated only with APG. Patients in the three groups were observed and the changes of related indexes were detected. [Results] After treatment, with regard to the three groups, the fasting blood glucose, 2-h postprandial blood glucose level, HbA1c, TNF-α, Hcy, blood urea nitrogen (BUN), creatinine (Cr) and 24-h urine protein levels were all decreased, yet AT-III level was increased, and granulation tissue coverage and thickness, wound clearance rate were increased, while the repair time of ulcer surface was significantly reduced. The above indexes were all significantly different (P<0.05). Compared with the control group C, the changes of the indexes in the study group A and B were the same as above, and the difference was significant (P<0.05). Compared with the study group A, the level of AT-III in group B was significantly increased (P<0.05), while TNF-α, Hcy, BUN, Cr and 24-h urine protein levels were significantly decreased (P<0.05). There was no significant difference in the other indexes between groups A and B (P>0.05). [Conclusions] Xuesaitong combined with APG could effectively reduce the blood sugar level of DF patients, improve the clinical indexes, promote wound healing, and the high-dose group had more significant advantages and was worthy of promotion.

Key words Diabetic foot, Xuesaitong, Autologous platelet-rich gel, Blood glucose, Antithromboplastin-III, 24-h urine protein level

1 Introduction

Diabetic foot (DF) is a kind of foot ulcer caused by distal nerve abnormality and angiopathy in patients with diabetes mellitus (DM) caused by long-term poor blood glucose control. The wound in the disease is difficult to heal due to repeated infection, poor local blood supply and other factors, and the treatment effect is not satisfactory. In severe cases, amputation is needed, so the quality of life of the patients is seriously affected[1-2]. Clinically, improving the blood circulation disorder of patients’ lower limbs is an important link to promote ulcer healing. Autologous platelet-rich gel (APG) is rich in growth factors and cytokines, which can reduce edema and promote ulcer healing[3], but the effect of APG alone is not significant. In this study, we combined Xuesaitong and APG, to determine the therapeutic effect of combined therapy on DF, so as to provide a scientific basis for patients with DF to choose a better treatment.

2 Data and methods

2.1 General information90 patients with diabetic foot treated in our hospital from February 2018 to July 2019 were randomly divided into study group A (n=30), group B (n=30) and control group C (n=30). In group A, there were 17 males and 13 females, aged from 43 to 83 years, with an average of (58.81±5.29) years. In group B, there were 16 males and 14 females, aged from 42 to 82 years, with an average of (57.23±5.36) years. In group C, there were 17 males and 13 females, aged from 43 to 80 years, with an average of (57.92±5.18) years. There was no significant difference in general data among the three groups (P>0.05).

2.2 Inclusion and exclusion criteriaInclusion criteria: the diagnostic symptoms of all patients met the diagnostic criteria of DF, Wagner grade II-IV, the study was approved by the hospital ethics committee, the patients or their families knew and signed the consent form[4].

Exclusion criteria: patients with type I diabetes complicated with urinary tract infection, systemic lupus erythematosus, chronic glomerulonephritis, acute glomerulonephritis, liver insufficiency and ulcers caused by other skin squamous cell carcinoma or malignant tumors were excluded.

2.3 MethodAutologous platelet-rich gel was prepared. Control group C: The patients were given routine blood glucose control, anti-infective drugs, lipid plaque stabilization, nutritional neurotherapy, and APG treatment at the same time. Study group B: On the basis of group C, patients were treated with high-dose Xuesaitong (Kunming Pharmaceutical Group Co., Ltd.; approval number: OTC Z20026438; specification: 400 mg), 400 mg/d, dissolved in 250 mL of 0.9% normal saline by intravenous drip. Study group A: On the basis of group C, patients were treated with low-dose Xuesaitong, 200 mg/d, dissolved in 250 mL of 0.9% normal saline by intravenous drip. All the three groups were treated continuously for 15 d.

2.4 Observed indexes4 mL of patients’ elbow vein blood was collected during fasting and 2 h after meal before and after treatment. Fasting blood glucose, 2-h postprandial blood glucose, BUN, Cr, Hcy and TNF-α were detected by Roche Cobas 8000 biochemical analyzer. 3 mL of elbow venous blood was collected from fasting patients, and HbA1c was detected by C501 module of Roche Cobas 8000 biochemical analyzer. 3 mL of elbow venous blood was collected from fasting patients. After plasma separation, AT-III was detected by CA5100 automatic hemagglutination analyzer (SYSMEX) chromogenic substrate assay. 24-h urine was collected and 24-h urine protein level was detected by C701 module of Roche Cobas 8000 biochemical analyzer.

The granulation tissue coverage rate, granulation tissue thickness, wound bacterial clearance rate and ulcer repair time were measured in the three groups after treatment.

3 Results and analysis

3.1 Detection of fasting blood glucose, 2-h postprandial blood glucose and HbA1cThe detection results of fasting blood glucose, 2-h postprandial blood glucose and HbA1c are shown in Table 1.

Table 1 Detection of fasting blood glucose, 2-h postprandial blood glucose and HbA1c n=30)

3.2 Detection of AT-III, TNF-α and Hcy(Table 2)

Table 2 Detection of AT-III, TNF-α and Hcy in plasma n=30)

3.3 Detection of BUN, Cr and 24-h urinary protein level(Table 3)

Table 3 Detection of BUN, Cr and 24-h urinary protein n=30)

3.4 Changes in the surface of foot ulcers(Table 4)

Table 4 Changes in the surface of foot ulcers n=30)

4 Discussion

Diabetic foot is a foot disease arising from peripheral neuropathy or vascular disease caused by long-term poor blood glucose control. The amputation rate of patients increases due to slow wound healing, and poor wound healing may be related to high glucose toxicity, local poor blood circulation caused by neurovascular diseases and other factors[5-6]. APG is a gel-like substance formed by centrifuging and concentrating patients’ peripheral venous blood into platelet-rich plasma mixed with thrombin-calcium. It can accelerate hemostasis, promote the repair and regeneration of wound and ulcer tissue[7-9]. It can promote the healing of ulcer surface in patients with DF, and has the advantages of convenient sampling, low risk and low cost[10-11]. However, the clinical effect is not satisfactory at present. Some studies have proposed that the clinical efficacy can be improved by combined use of drugs[12-13].

The results of this study showed that after treatment with Xuesaitong combined with autologous platelet-rich gel, fasting blood glucose, 2-h postprandial blood glucose, HbA1c, TNF-α, Hcy, blood urea nitrogen, creatinine and 24-h urinary protein levels in patients with diabetic foot were significantly decreased (P<0.05), while the content of AT-III in plasma was significantly increased (P<0.05). This showed that Xuesaitong combined with autologous platelet-rich gel had a significant clinical effect on patients with diabetic foot, and could significantly improve the level of blood glucose and related clinical indexes. Its mechanism may be related to the anti-ischemic injury, vasodilation, degradation of fibrinogen, inhibition of platelet adhesion and aggregation, and reduction of whole blood viscosity ofPanaxnotoginsengsaponins in Xuesaitong injection, therefore, it can effectively improve the microvascular dysfunction in patients with diabetes[14-17]. In addition, modern pharmacological studies have also confirmed thatP.notoginsengsaponins can scavenge excessive free radicals, protect the activity of endogenous antioxidant enzymes, and enhance tissue tolerance to hypoxia, thus reducing blood sugar, urinary protein and blood lipids[18-20].

In this study, compared with group A after treatment, the levels of TNF-α, Hcy, BUN, Cr and 24-h urinary protein in group B were significantly decreased (P<0.05). This showed that compared with the low-dose Xuesaitong group, the high-dose group had more advantages in reducing the clinical indexes of patients, so the use of high-dose Xuesaitong could achieve a better effect. After treatment, the granulation tissue coverage, granulation tissue thickness and wound clearance rate in group A and B were significantly higher than those in group C (P<0.05), and the ulcer repair time was significantly decreased (P<0.05). This showed that Xuesaitong combined with APG could reduce the repair time of foot ulcers and promote the recovery of patients. APG can provide growth factors and cytokines for ulcer recovery, promote fibroblast proliferation and vascular and subcutaneous tissue growth, and accelerate tissue repair, and gel texture can provide a moist environment for ulcer surface to reduce the risk of wound infection[10-11]. Based on the clinical efficacy of Xuesaitong mentioned earlier, it showed that APG combined with Xuesaitong could effectively reduce blood glucose, improve clinical indexes and promote foot ulcer wound repair in patients with diabetic foot, and the high dose group had more obvious advantages in improving clinical indexes.

To sum up, autologous platelet-rich gel combined with Xuesaitong could effectively reduce the level of blood glucose, improve clinical index and promote wound healing in patients with diabetic foot, and high-dose Xuesaitong had obvious advantages in improving patients’ clinical indexes, so it is recommended to popularize the use of Xuesaitong.